Objective: To compare some characteristics of two subgroups of tinnitus, noise-induced tinnitus and age-related tinnitus. Design: An online survey from the Iowa Tinnitus Website was reviewed. The participants were divided into two subgroups according to their reported cause of tinnitus—noise or aging. Their answers to the questions about loudness, qualities, worsening and reducing factors of tinnitus were analyzed. Study sample: There were 16 patients of age-related tinnitus and 147 of noise-induced tinnitus. Results: Two groups did not differ significantly in loudness (U = 887.5, p > 0.05), qualities (X2 = 1.164, p > 0.05) or reducing factors (X2 = 1.984, p > 0.05). Ringing/whistling was the most common quality of both age-related (37.5%) and noise-induced tinnitus (51.7%). 42.9% of participants of noise-induced tinnitus and 31.3% of age-related tinnitus felt that nothing made tinnitus better. The main worsening factors for noise-induced tinnitus included being in a noisy place (44.2%) and lack of sleep (42.9%) , which differed from the age-related group (X2 = 6.169, p < 0.05). Conclusions: There was a great deal of overlap between two subgroups, with some differences in worsening factors, including noise environment and lack of sleep. This is an important ‘red flag’ in counseling, and should be considered by doctors when choosing therapy.

Objectives The association between diagonal ear lobe crease (DELC) and cardiovascular disease was first suggested in 1973 although some studies have attributed this to confounding cardiovascular factors. This review looked to see if there is a significant association between DELC and angiography-confirmed coronary artery disease (CAD) independent of other risk factors. Design Systematic review and meta-analysis of selected studies using the PRISMA checklist. Setting 12 different hospitals with angiography in eight countries. Participants 4960 adult patients undergoing coronary angiography. Main Outcome Measures • Presence/absence of diagonal ear lobe crease • Diagnostic Odds Ratio • Sensitivity/Specificity Results 12 studies were included in the meta-analysis. Findings from our study suggest: • Patients with DELC have a 4x increased likelihood of having CAD (OR 4.61 P<0.00001). • The relationship between DELC and CAD was independent of age and all other conventional cardiovascular risk factors. • Bilateral DELC has a stronger association with CAD than unilateral DELC. • Presence of DELC has insufficient sensitivity / specificity to be used as a diagnostic test for cardiovascular disease but instead should be used as a risk marker. Conclusions We found that DELC is associated with CAD independently of other known cardiovascular risk factors including age. Histology studies indicate that atherosclerosis is causing DELC and patients with DELC appear to have an increased risk of CAD. It has insufficient sensitivity or specificity to be used as a diagnostic test but should be used as a valuable risk marker to be aware of whilst examining ears.

Abstract: Although there is plenty of research on the etiology and treatment of tinnitus, a definitive conclusion has not been reached in most studies. Among etiological factors, vascular and hematological abnormalities can be defined as an important cause in the evaluation of tinnitus cases, and these factors may underly many structural and functional problems. In this study, we aimed to investigate whether there was a correlation between platelet mass index (PMI) and tinnitus. To our knowledge, this is the first study exploring the effect of platelet mass on tinnitus. After reviewing the detailed medical records of 1,079 tinnitus patients that presented to our clinic between January 2019 and May 2020, the hemogram values of 177 cases meeting the study criteria were evaluated. There was no statistically significant difference between the patient and control groups in terms of mean age, gender distribution, and RBC (Red Blood Cell) neutrophil, lymphocyte, PLR and NLR levels (p>0.05). Compared to the control group, the hemoglobin and MPV levels of the patient group were statistically significantly higher (p<0.001), and the platelet level was statistically significantly lower (p=0.033). In addition, the PMI level of the patient group was significantly higher than that of the control group (p<0.001). In conclusion, the NLR, PLR and MPV values were found to be higher in the tinnitus group compared to the control group, as expected. Furthermore, the additional data for tinnitus cases showed that PMI was also observed to be significantly higher compared to the control group, indicating that the study objective was reached. PMI seems to be a predictive value for tinnitus, even in patients with MPV values lower than the normal range. Therefore, we consider that PMI is more sensitive than other markers, especially MPV in inflammatory events.

Phlegmariurus is a genus of lycophyte plants in the family Lycopodiaceae which is sensitive to climate change. In the past, there were four species namely 1) Phlegmariurus phlegmaria, 2) P. nummulariifolius, 3) P. carinatus, and 4) P. squarrosus found as epiphytic clubmosses on many trees such as pines and Agathis on the southern slope of Mt. Slamet. During 42 years there has been a significant loss of Phlegmariurus at the slope which covers approximately 15,000 ha rain forest covering the subdistrict of Cilongok in the west, Baturraden in the middle, and Sumbang in the east. Some surveys that had been conducted from 1978 to 2020 showed that the presence frequency of the plant decreased. We correlated the temperature increase data from NOAA and precipitaion data from the local meteorology and geophysics data to the frequency of the plants. Furthermore, we also interviewed ten nurseries which sold the Phlegmariurus of approximately 60 nurseries (Figure 6). The information we gathered showed that the location of the plant sources was above the previous locations. We also observed the cultivated Phlegmariurus at different altitudes namely at 95-97 m, 300-400 m, and 600-800 m a.s.l. The result of this study showed that in the past there were a lot of Phlegmariurus spp. However, in 2020 Phlegmariurus were absent in most areas at the southern slope of Mt. Slamet. We proposed three causes of the migration and loss of Phlegmariurus at the southern part of Mt. Slamet namely: 1) The increase of temperature, the decrease of precipitation, and 3) commercial hunting.

Following a preliminary investigation a study was carried from April to October, 2019 to establish more information on the abundance and distribution of freshwater snails in relation to physiochemical factors of Warwade dam. Four sampling sites; human activity, vegetation cover, lentic and lotic were selected for the study along the bank of the dam. Freshwater snails were collected in each of the four sampling sites using long handled scoop net with mesh 0.2mm and hand picking methods. Water samples from the sampling sites were analyzed in the laboratory using standard procedures. A total of 2,027 of fresh water snails belonging to ten species were identified with Bulinus globosus 12(0.6%) and Lymnaea natalensis 12(0.6%) having the lowest abundance while Melanoides tuberculata 1553(76.6%) had the highest. Snail abundance was highest in site characterized by human activities (670) followed by vegetation (482), lotic (442) and lentic (433) waters. Most of the physico-chemical factors measured appeared to favour the growth and survival of fresh water snails. pH (p = 0.01), water current (p = <0.01) and magnesium ion concentration (p = < 0.01) varied significantly across the four sites. Only calcium ion concentration was significantly associated with snail abundance (p = 0.04). Snail abundance showed weak positive relationship with water temperature, color, turbidity and concentration of magnesium ion. The dominance of M. tuberculata over all species particularly those of medical and veterinary importance could have positive implication for their control in the dam.

Araneid spiders use abstract color patterns to attract prey. The chromatic properties of these displays vary extensively, both within and across species, and they are frequently polymorphic. Variation is often expressed in terms of signal hue (color per se), but it is unclear precisely how attractiveness scales with this property. We assessed captures among color-manipulated females of the dimorphic jeweled spider Gasteracantha fornicata in their natural webs. The manipulation magnified the natural variation in stimulus hue independently of chroma (saturation) across a range spanning most of the color spectrum. Catch rate varied across treatments in simple accordance with how greatly stimulus hue deviated from either of the two extant phenotypes. Predictions based upon fly-perceived background contrast were unsupported despite dipterans constituting ~60 % of prey. This study isolates the importance of stimulus hue and supports the premise that extant phenotypes reside in an optimal spectral range for prey attraction.

• The UK National Institute for Health and Care Excellence has estimated a 70% increase in demand resulting from the 2019 modification to cochlear implant criteria • We modelled the projected increase using our large database of pure tone audiometry results, and adjusted for frailty as a marker of risk of general anaesthesia • Our results suggest an overall 79% increase in demand, with most of this for adult implantation, and in particular for those over the age of 65 • Our findings are important for those planning delivery of cochlear implant services

In the 2001 film Zoolander, the lead character, played by Ben Stiller, ditches his old “Blue Steel” look and develops an exciting new ‘Magnum” look that the fashion industry enthusiastically embraces. The evil mastermind, Mr Mugato, played by Will Farrell, exclaims “The man has only one look, for Christ’s sake! … They’re the same face! Doesn’t anybody notice this? I feel like I’m taking crazy pills!” We argue here that eco-evolution is the “Magnum” of biology: it is fashionable, lots of people love it, but it is not new. We also argue that, like the “Blue Steel” look in the 2016 sequel, Zoolander 2, eco-evolution is being seen where it does not belong.

Aim: The aim of the study was to compare the outcomes of emergent and planned peripartum hysterectomy. Methods: This retrospective cross-sectional study was conducted in two hospitals. Maternal and neonatal outcomes were compared according to the emergent and planned peripartum hysterectomy. Results: Totally 34020 deliveries were evaluated retrospectively and 66 peripartum hysterectomy cases were analyzed. Of these patients, 31 cases were planned surgery and 35 cases were emergent surgery. The patients who underwent planned peripartum hysterectomy had lower rate of blood transfusion (83.9% vs. 100%, p=0.014), higher postoperative hemoglobin levels (9.9±1.3 vs. 8.3±1.3, p<0.001) compared with the emergent hysterectomy group. The birth weight was lower although the apgar scores were higher in the planned surgery compared with the emergent cases. Conclusion: The planned peripartum hysterectomy with a experienced team provide less need for transfusion and improved neonatal outcomes in regard to the emergent peripartum hysterectomy.

Background The high mutation rate of influenza A virus hemagglutinin segment brings great challenges to its long-term effective testing and subtyping. Method We analyzed the conserved sequences of hemagglutinin subtype H1-H9 by breadth first, and designed primers for HA subtyping based on conserved sequences. Results Our conserved sequence searching method get high specificity conserved sequences on H1-H9 subtypes respectively. And PCR experiments show that primers based on conserved sequences can be used in influenza A virus HA subtyping. Conclusions Conserved sequences based primers are expected to be the long-term effective influenza A virus HA subtyping tools.

Background & aims: According to the recommendation of the Centers for Disease Control and Prevention (CDC), getting Influenza Vaccines during the Coronavirus (COVID-19) pandemics is especially important for people with certain underlying medical conditions, like cancer. Due to the similarities between the symptoms of influenza and Covid-19, receiving the flu vaccine in suspicious cases can be helpful because it will make it easier to request a medical test and diagnosis. In this cross-sectional descriptive study, the value of influenza vaccination in the cancer population was investigated. Subjects and Methods: All cancer patients who were referred to our clinic and had eligibility to receive the flu vaccine were included in our study for following up clinical signs every week for one month. All patients who were vaccinated from October 1 to 15, 2020, were investigated. The most side effects that were followed were fever, runny nose, bone pain, life-threatening, or persistent adverse effects. Results: From a total of 289 patients [median age: 52 years (range 18-79), 112 (38.9 %) males and 176 (61.1%) female] with different types of cancers, only two patients had an adverse effect of vaccination (including bone pain, runny nose, and fatigue), and one had Covid-19 ten days after vaccination. The rest of the patients did not show any side effects due to flu vaccination after one month of follow-up.

The A.nanchuanensis (Artocarpus Nanchuanensis, Moraceae) is an evergreen Artocarpus genus representative tree species in the northernmost natural distribution and one of the extremely endangered tree species in China. In this study, we obtained a high-quality chromosome-scale genome assembly and annotation for A.nanchuanensis using inter-grated approaches, including Illumina, Nanopore sequencing platform as well as Hi-C. A total of 128.71 gigabases (Gb) raw Nanopore Sequel reads were generated from 20 kb libraries. After filtering, 123.38 Gb clean reads were obtained, giving 160.34x coverage depth. The final assembled A.nanchuanensis genome was 769.44 Mb with a contig N50 of 2.09 Mb, and 99.62% (766.50 Mb) of the assembly data was assigned to 28 pseudochromosomes. Gene modelling predicted 41,636 protein-coding genes, of which 95.10% were annotated. The gene annotation completeness was evaluated by BUSCO, and 94.44% conserved genes could be found in the assembly data. The disclosure of A.nanchuanensis genome sequence information provides an important resource to expand our understanding of the molecular mechanism in its unique biological processes and nutritional, medicinal benefits.

Giant superior vena cava (SVC) aneurysm in obstructive supracardiac total anomalous venous connection (TAPVC) is rare, and there has not been a giant SVC aneurysm reported in non-obstructive TAPVC. Here we reported a 29‐year‐old female with non-obstructive TAPVC and a giant SVC aneurysm. Routine TAPVC correction and partial venoctomy were done, considering that such a giant aneurysm in a non-obstructive venous arch might have its histological etiology and higher risk of thrombosis and/or rupture.

DNA barcodes are standardized sequences that range between 400-800 bp, vary at different taxonomic levels, and make it possible to identify individuals of species that have been previously assigned taxonomically. Several barcodes have been identified in different groups in the tree of life. However, there are groups that lack an accurate DNA marker, and even more so, accurate strategies that enable verification of their taxonomic affiliation. Several DNA barcodes have been postulated for plants, nonetheless, their classification potential has not been evaluated for metabarcoding, and as a result, it would appear as no one of them excels above the others in this area. One tool that has recently gained traction is Naïve Bayesian Classifiers; this type of classifier is based on the independence of attributes and the allocation of categories in each context. The present study aims at evaluating the classification power of several plant genetic markers that have been proposed as barcodes (trnL, rpoB, rbcL, matK, psbA-trnH and psbK) using a Naïve Bayesian Classifier, in order to determine the markers with higher performance at different taxonomic levels for metabarcoding analysis and to identify problematic genera at the time of species assignment. We propose matK and trnL as potential candidates up to the genus assignment. Some problematic genera (Aegilops, Gueldenstaedtia, Helianthus, Oryza, Shorea, Thysananthus and Triticum) within certain families in a sample could lead to misclassification no matter which marker is used. Finally, we propose recommendations when performing taxonomic identification analysis of plants in samples with multiple individuals.

Interleukin-31 has been implicated in the pathophysiology of multiple atopic disorders such as atopic dermatitis (AD), rhinitis and airway hyperreactivity. In AD, IL-31 has been identified as one of the main ‘drivers’ of its cardinal symptom pruritus. Here, we aim to summarize the mechanisms by which IL-31 modulates inflammatory and allergic diseases. TH2 cells play a central role in AD and release high levels of TH2-produced cytokines including IL-31, thereby mediating inflammatory responses, initiating immunoregulatory circuits, and stimulating itch and neuronal outgrowth through activation of the heterodimer receptor IL-31 receptor alpha (IL31RA)/Oncostatin M receptor β. IL31RA expression is found on human and murine dorsal root ganglia neurons, epithelial cells including keratinocytes as well as various innate immune cells. IL-31 is a critical cytokine involved in neuro-immune communication, which opens new avenues for cytokine modulation in neuroinflammatory diseases including AD/pruritus, as validated by recent clinical trials using an anti-IL-31 antibody. Accordingly, inhibition of IL-31 downstream signaling may be a beneficial approach for various inflammatory diseases including prurigo nodularis. For example, whether downstream JAK inhibitors directly block IL-31-mediated-signaling needs to be clarified. Targeting the IL-31/IL31RA/OSMRβ axis appears to be a promising approach for inflammatory, neuroinflammatory and pruritic disorders in the future.

The incidence of prosthetic valve thrombosis post transcatheter mitral valve replacement remains largely unknown. Although it may occur more frequently than after transcatheter aortic valve replacement, only isolated cases have been reported up to now. This unique large mushroom thrombus post TMVR case is first of its kind reported ever. 3D transesophageal as well as transthoracic echocardiography play very important role in early diagnosis and for treatment decision

Soil moisture is essential for vegetation restoration in arid and semi-arid regions. Ascertaining the vertical distribution and transportation of soil moisture under different vegetation restoration types has a profound impact on the ecological construction. In this study, the soil moisture at a depth of 500 cm for four typical vegetation types, including R. pseudoacacia (forestland), C. korshinskii (shrubland), S. bungeana (abandoned land), and corn (cropland) were investigated and compared in the Zhifanggou watershed of Loess plateau, China. Additionally, hydrogen and oxygen stable isotopes were detected to identify and reflect the characteristics of soil water. The results showed vertical distribution and transportation of soil moisture have different variations under different vegetation types. Depth-averaged soil moisture under S. bungeana and corn increased along the profile as a whole, while C. korshinskii and R. pseudoacacia showing a trend of weakly increasing and relatively stable state after an obvious decreasing trend (0–40 cm). The mean soil moisture under R. pseudoacacia is lower than other types, especially in deeper layers. In addition, it was observed that the longer vegetation age, the lower mean soil moisture, while this phenomenon was unobvious in S. bungeana. Planting arbor species such as R. pseudoacacia intensified the decline of soil moisture in the Loess Plateau, this limited the growth of arbor species in turn. The capacity of evaporation fractionation of soil moisture followed the sequence: corn > S. bungeana > R. pseudoacacia > C. korshinskii. Profiles of δ18O values of soil moisture under different vegetation types are quite different. On the whole, the δ18O values varied greatly in upper soil layers and tend to be consistent with the increase of soil depth. We estimate that piston flow is the main mode of precipitation infiltration, and the occurrence of preferential flow is related to vegetation types. These results are expected to help improve the understanding of the response of deep soil moisture to vegetation restoration and inform practices for sustainable water management.

Concentration–discharge (C–Q) relationships are widely used to assess the link between hydrological and biogeochemical processes at catchment scale. They can be fitted to represent either concentrations or discharge-weighted concentrations (i.e., load). In this technical note, we test a multi-objective calibration using both concentration and load, and compare it to a mono-objective calibration applied on either concentrations or load: although widely used in hydrological modeling, multi-objective calibrations are rarely applied to fit C–Q relationships. The multi-objective calibration yielded parameters which were more representative of the concentration behavior during the rarest high-flow events, avoiding issues of under-representation of high-discharge, low-concentration periods. In this technical note, we use the multi-objective calibration on a high-frequency dataset acquired on the ORACLE-Orgeval Observatory (France).

In many instances, dynamic, potential status and geochemical characteristics of groundwater discharging through natural springs are not well known. Present study has assessed the deep groundwater in the form of thermal and non-thermal spring in artesian condition in the selected zones in Sri Lanka, using isotope and geochemical characteristics. The results revealed that evaporation-fractional crystallization and cation-exchange in the sedimentary aquifers while rock-water interaction in crystalline deep aquifers, are the significant mechanism that control the groundwater chemistry. All the deep groundwater recharged from meteoric water at different elevations and further influenced by either evaporation or rock-water interaction during the subsurface flow. Artesian aquifers in the sedimentary terrain in the north-western coastal zones showed the recharging elevation as from 100 to 200 m amsl. They are not mixed with sea water and slightly impacted by the locally evaporated surface waters. Almost all these waters are comparatively old; indicating slow movement along the regional flow paths. Considering the recharge and discharge conditions of artesian non-thermal waters in the Southern lowlands of crystalline terrain can be classified as non-mixed, non-evaporated and young groundwater with higher elevation recharge. The artesian non-thermal waters in the East North Central lowlands, have shown the same characteristics but with evaporated conditions. All artesian thermal waters are tritium free, hence they are older and deep percolated. Intensive rock-water interaction and higher altitude origin were observed in some thermal springs. Some spring clusters in the weathered overburden have shown significant mixing with recent local rains. Non-mixed, non-evaporated and less rock-water interacted nature is a significant in two thermal springs that emerges through (chemically inert) quartzite bed rock. Both thermal and non-thermal water with artesian condition have clearly indicated that they are originated from a common recharge source but with different flow paths in different penetration depths and travel distances, resulting different chemical characteristics. Fresh water springs are mostly young and recharged from local rains followed with shallow percolation.

Welded joints are widely employed in engineering field and they are always the starting points of fatigue damage. Because of the unfavorable material and geometry characters, as well as initial welding defects, the fatigue damage evaluation of welded joints is an important and troublesome issue for engineers. In this article, multiaxial fatigue space theory proposed by the first author for smooth specimens is extended for the fatigue damage assessment of welded joints, by adopting nominal stress approach. The fatigue test data with different materials, loading paths, and welded joints geometries are used to validate the capability of this theory. The result indicates a strong parallelization between predicted life and experimental life, with a favorable prediction error and beneficial error distribution. It can be concluded that multiaxial fatigue space theory is a useful method for fatigue damage assessment of welded joints with the help of nominal stress approach.

Objectives: To externally validate the demographic setting of the online Fetal Medicine Foundation (FMF) Stillbirth Risk Calculator based upon maternal medical and obstetric history in a case-matched cohort. Design: Retrospective case-control study Setting: Tertiary referral hospital Population: 144 fetuses after singleton intrauterine fetal death (IUFD) and a matched control group of 247 singleton live births between 2003 and 2019 Methods: Nonparametric receiver operating characteristics (ROC) analysis was performed to predict the prognostic power of the risk score and to generate a cut-off value to discriminate best between the events of stillbirth versus live birth. Main Outcome Measures: FMF Stillbirth risk score Results: The IUFD cohort conveyed a significantly higher overall risk assessment with a median FMF Stillbirth risk score of 0.45% (0.19-5.70%) compared to live births [0.23% (0.18-1.30%); p<0.001]. Demographic factors mainly contributing to the increased risk were BMI (p=0.002), smoking (p<0.001), chronic hypertension (p=0.015), APS (p=0.017), type 2 diabetes (p<0.001) and need for insulin (p<0.001). ROC analysis to evaluate the discriminative ability of the FMF Stillbirth Risk Calculator showed an area under the curve (AUC) of 0.72 (95% CI 0.67–0.78; p<0.001). The FMF Stillbirth risk score at a cut-off level of 0.34% (OR 6.22; 95% CI 3.91–9.89; p<0.001) yielded a specificity of 82% and a sensitivity of 58% in predicting singleton antepartum stillbirths. Conclusion: The FMF Stillbirth Risk Calculator achieved a similar performance in our cohort of women as in the reference group.

Proverbs exist in every nation's language and it is one of the vehicles carrying her culture. Proverbs do not only reflect people's ideas and thoughts but also preserve their world view and values in traditional society. This paper analyzes sexism found in Chinese and Igbo proverbs. Prejudice or discrimination against women exists in both Chinese and Igbo proverbs, mainly on female social status, marriage, cultural responsibility, behavior, and personality. Some of these proverbs intend to portray women as weak, chattering, gossipers, nosy, and of low social status. Others emphasize that women have bad-temperament and are acrimonious, which are not easy to cope with, and if women are in charge, things will be out of order. In marriage, the husband dominates and dictates the fate of the wife. The reasons for gender discrimination in Igbo and Chinese are due to cultural/traditional values, socioeconomic development, gender identity, and physiological factors. However, due to globalization and awareness creation, there are trends in female gender consciousness and awakening in China and Nigeria.

Exceeding thermal thresholds causes irreversible damage and ultimately loss of leaves. The lowland tropics are among the warmest forested biomes, but little is known about heat tolerance of tropical forest species. We surveyed leaf heat tolerance of sun-exposed leaves from 147 tropical lowland and pre-montane forest species by determining the temperatures at which potential photosystem II efficiency based on chlorophyll a fluorescence started to decrease (TCrit) and had decreased by 50% (T50). TCrit averaged 46.7°C (5th–95th percentile: 43.5–49.7°C) and T50 averaged 49.9°C (47.8–52.5°C). Heat tolerance partially adjusted to site temperature; TCrit and T50 decreased with elevation by 0.40°C and 0.26°C per 100m, respectively, while mean annual temperature decreased by 0.63°C per 100m. The phylogenetic signal in heat tolerance was weak, suggesting that heat tolerance is more strongly controlled by environment than by evolutionary legacies. TCrit increased with the estimated thermal time constant of the leaves, indicating that species with thermally buffered leaves maintain higher heat tolerance. Among lowland species, T50 increased with leaf mass per area, so species with structurally more costly leaves reduce the risk of leaf loss during hot spells. These results provide insight in interspecific variation in heat tolerance at local and regional scales.

The global pandemic outbreak, SARS-COV-2, which causes COVID-19, has coerced numerous pharmaceutical companies to sprint for the vaccine and therapeutic biologics development. Most of the therapeutic biologics are common human IgG antibodies, which were identified by next-generation sequencing with the B cells from the convalescent patients in less than one-month post-infection. While the global public health emergency calls for medications urgently, it saves lives to expedite the clinical trials of biologics as much as possible, hence the biologics development strategies are unprecedentedly challenged. Since the advent of therapeutic biologics, transfection, and selection strategy has been continuously improving for developing more robust cell lines with greater productivity and efficiency. Next-generation sequencing (NGS) has also been implemented into cell bank testing for acceleration. These recent advances enable us to rethink and reshape the chemistry, manufacturing and controls (CMC) strategy against the pandemic outbreaks, to start supplying cGMP materials for the life-saving clinical trials as soon as possible. We elucidated an accelerated CMC workflow for biologics against pandemics, including using cGMP-compliant pool materials for Phase I clinical trials, selecting the final clone with similar product quality as Phase I materials for late-stage development and commercial production and matching product quality among different manufacturing stages.