bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent High Burden and Mortality Associated With Advanced HIV Disease in Rural Tanzania Despite Uptake of World Health Organization “Test and Treat” Guidelines
Authors: Stöger Linda , Katende Andrew , Mapesi Herry , Kalinjuma Aneth V , van Essen Liselot , Klimkait Thomas , Battegay Manuel , Weisser Maja , Letang Emilio
Published: December 2022

Background

Information about burden, characteristics, predictors, and outcomes of advanced human immunodeficiency virus disease (AHD) is scarce in rural settings of sub-Saharan Africa. Human immunodeficiency virus (HIV) infections and associated deaths remain high despite specific guidelines issued by the World Health Organization (WHO).

Methods

Burden of AHD and 6-month death/loss to follow-up (LTFU) were described among 2498 antiretroviral therapy (ART)–naive nonpregnant people with HIV (PWH) aged >15 years enrolled in the Kilombero Ulanga Antiretroviral Cohort in rural Tanzania between 2013 and 2019. Baseline characteristics associated with AHD and predictors of death/LTFU among those with AHD were analyzed using multivariate logistic and Cox regression, respectively.

Results

Of the PWH, 62.2% had AHD at diagnosis (66.8% before vs 55.7% after national uptake of WHO “test and treat” guidelines in 2016). At baseline, older age, male sex, lower body mass index, elevated aminotransferase aspartate levels, severe anemia, tachycardia, decreased glomerular filtration rate, clinical complaints, impaired functional status, and enrollment into care before 2018 were independently associated with AHD. Among people with AHD, incidence of mortality, and LTFU were 16 and 34 per 100 person-years, respectively. WHO clinical stage 3 or 4, CD4 counts <100 cells/µL, severe anemia, tachypnea, and liver disease were associated with death/LTFU.

Conclusions

More than 50% of PWH enrolled in our cohort after test and treat implementation still had AHD at diagnosis. Increasing HIV testing and uptake and implementation of the WHO-specific guidelines on AHD for prevention, diagnosis, treatment of opportunistic infections, and reducing the risks of LTFU are urgently needed to reduce morbidity and mortality.
Human Immunodeficiency Virus Type 1 RNA Genital Tract Shedding After Cryotherapy for Cervical Intraepithelial Neoplasia in Western Kenya
Authors: Orang’o Elkanah Omenge , Bocage Anne E , Liu Tao D , Itsura Peter M , Tonui Philip K , Muthoka Kapten , Stephen Kiptoo , Caliendo Angela M , Sam Soya S , Cu-Uvin Susan
Published: December 2022

This prospective study of 39 women living with human immunodeficiency virus (HIV) on antiretroviral therapy in Western Kenya aimed to quantify genital tract HIV-1 RNA (GT-HIV RNA) shedding before and after cryotherapy for cervical intraepithelial neoplasia. Most GT-HIV RNA shedding was detected precryotherapy, suggesting that cryotherapy was not the primary cause of shedding.
Knockout ofOsSWEET15Impairs Rice Embryo Formation and Seed-Setting
Authors: Hu Zhi , Tang Zhenjia , Yang Jing , Bao Shuhui , Zhang Yuanyuan , Ma Lai , Zheng Qingsong , Yang Fang , Zhang Dechun , Sun Shubin , Hu Yibing
Published: December 2022

We show that the knockout of a sugar transporter gene OsSWEET15 led to a significant drop in rice fertility with around half of the knockout mutant’s spikelets bearing blighted or empty grains. The rest of the spikelets bore fertile grains with a slightly reduced weight. Notably, the ovaries in the blighted grains of the ossweet15 mutants expanded after flowering but terminated their development before the endosperm cellularization stage and subsequently aborted. β- glucuronidase (GUS) and Green Fluorescent Protein (GFP) reporter lines representing the OsSWEET15 expression showed that the gene was expressed in the endosperm tissues surrounding the embryo, which supposedly supplies nutrients to sustain embryo development. These results together with the protein’s demonstrated sucrose transport capacity and plasma membrane localization suggest that OsSWEET15 plays a prominent role during the caryopsis formation stage, probably by releasing sucrose from the endosperm to support embryo development. By contrast, the empty grains were probably caused by the reduced pollen viability of the ossweet15 mutants. Investigation of ossweet11 mutant grains revealed similar phenotypes to those observed in the ossweet15 mutants. These results indicate that both OsSWEET15 and OsSWEET11 play important and similar roles in rice pollen development, caryopsis formation and seed-setting, in addition to their function in seed-filling that was demonstrated previously.
Characteristics of Population-Based Practice in Physical Therapy
Authors: Giuffre Suzanne , Keehan Jane , Ruffing Stacy , Domholdt Elizabeth , Van De Carr Terri
Published: December 2022

Objective

Physical therapy is placing new emphasis on how the profession might contribute to improving population health. However, little is known about the nature of population-based practice (PBP) of physical therapists. Therefore, the purpose of this study was to develop a view of PBP from the perspective of physical therapists engaged in it.

Methods

Twenty-one physical therapists participating in PBP were interviewed. Qualitative descriptive analysis was used to summarize results.

Results

Most of the reported PBP was at the community and individual level, and the most common types of PBP were health teaching and coaching, collaboration and consultation, and screening and outreach. Three topic areas were identified (with respective themes): characteristics of PBP (meeting group or community needs, promotion and prevention, access, and movement), preparation for PBP (core vs elective, experiential learning, social determinants of health, and health behavior change), and rewards and challenges of PBP (intrinsic rewards, funding and resources, professional recognition, and complexity of behavior change).

Conclusion

PBP in physical therapy presents practitioners with rewards and challenges as they work to improve the health of populations.

Impact

Physical therapists who are currently engaged in PBP are, in effect, defining the role of the profession in improving health at a population level. The information in this paper will help the profession move from a theoretical view of the role of physical therapists in improving population health to understanding what this role looks like in practice.
Superstable homogeneous lipiodol–ICG formulation: initial feasibility and first-in-human clinical application for ruptured hepatocellular carcinoma
Authors: Xiong Yongfu , He Pan , Zhang Yang , Chen Hu , Peng Yisheng , He Peng , Tian Jie , Cheng Hongwei , Liu Gang , Li Jingdong
Published: December 2022

The most common treatment of spontaneous tumor rupture hemorrhage (STRH) is transcatheter arterial embolization (TAE) followed by liver resection, and surgical navigation using near-infrared fluorescence is effective method for detecting hidden lesions and ill-defined tumor boundaries. However, due to the blockage of the tumor-supplying artery after effective TAE treatment, it is difficult to deliver sufficient fluorescent probes to the tumor region. In this study, we report on the successful application of superstable homogeneous intermixed formulation technology (SHIFT) in precise conversion hepatectomy for ruptured hepatocellular carcinoma (HCC). A homogeneous lipiodol–ICG formulation obtained by SHIFT (SHIFT-ICG) was developed for clinical practice for STRH. A ruptured HCC patient received the combined protocol for embolization and fluorescence surgical navigation and exhibited excellent hemostatic effect. Lipiodol and ICG were both effectively deposited in the primary lesion, including a small metastatic lesion. In follow-up laparoscopic hepatectomy, SHIFT-ICG could clearly and precisely image the full tumor regions and boundaries in real time, and even indistinguishable satellite lesions still expressed a remarkable fluorescence intensity. In conclusion, the simple and green SHIFT-ICG formulation can be effectively used in emergency embolization hemostasis and later precise fluorescence navigation hepatectomy in patients with ruptured HCC bleeding and has high clinical application value.
Inimical impact of high-fat diet on expression of heme oxygenase-1, trace metals content, and associated intestinal histopathology
Authors: Sheikh Nadeem , Shakeel Shakira , Akhtar Tasleem , Khawar Muhammad Babar
Published: December 2022

A high-fat diet (HFD) is one of the most prominent causative factors for obesity and metabolic inflammation. The effects of HFD overconsumption on intestinal histology, expression of haem oxygenase-1 (HO-1), and transferrin receptor-2 (TFR2) remain elusive. The present study was conducted to analyze the effect of HFD on these parameters. To develop the HFD-induced obese model, rat colonies were divided into 3 groups; the control group was reared on normal rat chow, whereas groups I and II were given HFD for 16 weeks. Hematoxylin and eosin (H & E) staining revealed marked epithelial changes, inflammatory cell infiltrates, and destruction of mucosal architecture in both experimental groups as compared to the control group. Sudan Black B staining showed a high triglyceride deposition in the intestinal mucosa of animals fed on HFD. Atomic absorption spectroscopy revealed a decrease in tissue copper (Cu) and selenium (Se) concentration in both HFD experimental groups. Whereas the cobalt (Co) and manganese (Mn) levels were comparable to controls. The mRNA expression levels of HO-1 and TFR2 were found to be significantly upregulated in HFD groups compared to the control group. Hence, HFD consumption leads to histopathological changes and altered gene expression in the rodent intestine. So, one should remove HFD from daily meals to avoid related metabolic complications.
Traumatic Life Experience and Pain Sensitization
Authors: Nanavaty Namrata , Thompson Christopher G. , Meagher Mary W. , McCord Carly , Mathur Vani A.
Published: December 2022

Objectives:

Psychological trauma often co-occurs with pain. This relationship has been explored using laboratory pain measures; however, findings have been mixed. Previous studies have limited operationalization of trauma (eg, posttraumatic stress disorder) or pain (eg, pain thresholds), which may contribute to conflicting results. Further, prior reviews likely underrepresent trauma experiences among people who are not receiving clinical care, limiting generalizability.

Materials and Methods:

We systematically reviewed the existing literature on the relationship between psychological trauma (eg, car accidents, sexual assault, childhood abuse, neglect) and laboratory pain (ie, quantitative sensory testing measures of pain threshold, intensity, summation, modulation), using inclusive criteria. The direction of the relationship between psychological trauma and pain sensitivity was evaluated, and moderation by purported pain mechanism (ie, pain detection, suprathreshold pain, central sensitization, inhibition) was explored.

Results:

Analyses were conducted using 48 studies that provided 147 effect sizes. A multivariate random-effects model with robust variance estimation resulted in a small but statistically significant overall effect size of g=0.24 (P=0.0002), reflecting a positive association between psychological trauma and enhanced laboratory pain sensitivity. Upon examination of mechanistic moderators, this relationship appears driven by effects on pain detection (g=0.28, P=0.002) and central sensitization (g=0.22, P=0.04). While effect sizes were similar across all moderators, effects on suprathreshold pain and inhibition were not statistically significant.

Discussion:

Findings demonstrate an overall pattern of trauma-related pain enhancement and point to central sensitization as a key underlying mechanism.
Major Publications in the Critical Care Pharmacotherapy Literature: 2021
Authors: Wieruszewski Patrick M. , Brickett Laura M. , Dayal Lokesh , Egan Ashley M. , Khanna Ashish K. , Lemieux Steven M. , Mukkera Satyanarayana R. , Patel Jaimini S. , Reichert Michael J. , Reynolds Tessa R. , Sen Parijat , Thornton Nathaniel M. , Turpin Gavin M. , Winter Jessica B. , Bissell Brittany D.
Published: December 2022

OBJECTIVES:

To summarize the most impactful articles relevant to the pharmacotherapy of critically ill adult patients published in 2021.

DATA SOURCE:

PubMed/MEDLINE.

STUDY SELECTION:

Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critical care patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2021, and December 31, 2021.

DATA EXTRACTION:

Candidate articles were organized by clinical domain based on the emerging themes from all studies. A modified Delphi process was applied to obtain consensus on the most impactful publication within each clinical domain based on overall contribution to scientific knowledge and novelty to the literature.

DATA SYNTHESIS:

The search revealed 830 articles, of which 766 were excluded leaving 64 candidate articles for the Delphi process. These 64 articles were organized by clinical domain including: emergency/neurology, cardiopulmonary, nephrology/fluids, infectious diseases, metabolic, immunomodulation, and nutrition/gastroenterology. Each domain required the a priori defined three Delphi rounds. The resultant most impactful articles from each domain included five randomized controlled trials and two systematic review/meta-analyses. Topics studied included sedation during mechanical ventilation, anticoagulation in COVID-19, extended infusion beta-lactams, interleukin-6 antagonists in COVID-19, balanced crystalloid resuscitation, vitamin C/thiamine/hydrocortisone in sepsis, and promotility agents during enteral feeding.

CONCLUSIONS:

This synoptic review provides a summary and perspective of the most impactful articles relevant to the pharmacotherapy of critically ill adults published in 2021.
Structural and Functional Brain Alterations in Populations with Familial Risk for Depression: A Narrative Review
Authors: Burhanoglu Birce Begum , Gonul Ali Saffet
Published: December 2022

Learning objectives

After completing this activity, practitioners will be better able to:

• Discuss the association between brain alterations and vulnerability or resilience to MDD in people with familial risk

• Define how structural and functional brain alterations associated with vulnerability or resilience could lead to a better understanding of the pathophysiology of MDD

Aim

Familial history is associated with an increased risk for major depressive disorder (MDD). Despite the increased risk, some members of the familial high-risk population remain healthy, that is, resilient. Defining the structural and functional brain alterations associated with vulnerability or resilience could lead to a better understanding of the pathophysiology of MDD. This study aimed to review the current literature and discuss the association between brain alterations and vulnerability or resilience to MDD in people with familial risk.

Methods

A literature search on MRI studies investigating structural and functional alterations in populations at familial risk for MDD was performed using the PubMed and SCOPUS databases. The search was conducted through June 13, 2022.

Results

We reviewed and summarized the data of 72 articles (25 structural MRI, 35 functional MRI, 10 resting-state fMRI, one structural/functional MRI combined, and one structural/functional/resting-state fMRI combined). These findings suggested that resilience in high-risk individuals is related to the amygdala structure, frontal lobe activity, and functional connectivity between the amygdala and multiple frontal regions.

Conclusion

Resilient and vulnerable individuals exhibit structural and functional differences in multiple frontal and limbic regions. However, further systematic longitudinal research incorporating environmental factors is required to validate the current findings.
Natural Chinese herbs for the prevention and treatment of acute pancreatitis: a narrative review
Authors: Cui Jiaqi , Wu Di , Zhou Huimin , Chen Haiyan , Dong Zhixia , Yang Jun
Published: December 2022

Acute pancreatitis (AP) is a disease characterized by local inflammation in the pancreas, followed by trypsin activation, and may result from multiple etiologies. Approximately 20% of AP can progress to severe acute pancreatitis (SAP), which can lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS). SAP mortality rates have remained high in recent years, but there are currently no specific drugs designed to reduce these rates. Clinical studies have shown that patients can reduce the symptoms of the disease and slow down the development of the disease after taking the Chinese medicine decoction. Basic studies have shown that in AP or SAP disease models, the use of Chinese medicine monomers can improve the condition of rates. These natural Chinese herbal products can improve pancreatitis, given their ability to act on multiple targets. However, they have not been widely employed clinically and studied sufficiently and thoroughly. Therefore, this review aimed to summarize the pathophysiological mechanisms underlying pancreatitis and review the potential role of natural Chinese herbs (monomers and decoctions) in clinical and basic research.
Correlative factor of death in patients with infected pancreatic necrosis after surgical intervention
Authors: Chen Yuhui , Liu Zhiwei , Cai Shouwang
Published: December 2022

Background:

Acute pancreatitis (AP) was a potentially fatal disease with a variation in severity. Infected pancreatic necrosis was a common complication in AP which needed surgical intervention. The present study was to study the correlative factors of death in patients with infected pancreatic necrosis after surgical intervention.

Methods:

From January 2016 to October 2019, a total of 186 patients with infected pancreatic necrosis after surgical intervention in the First Medical Center, Chinese PLA General Hospital were retrospectively enrolled in this study. Of the 186 patients, 22 who died in the hospital were defined as a mortality group and the others as a survival group. The clinical characteristic of the 2 groups was compared and the relative risk of mortality in patients with infected pancreatic necrosis after the surgical intervention was studied.

Results:

Acute fluid collection, acute kidney injury, acute lung injury, acute liver injury, multiple organ dysfunction syndromes, abdominal bleeding, abdominal Acinetobacter baumannii infection, pulmonary infection, pulmonary A baumannii infection, positive blood culture, A baumannii of blood culture, severe acute pancreatitis according to Atlanta 2012, the use of continuous renal replacement therapy, mechanical ventilation and minimally invasive retroperitoneal pancreatic necrosectomy was associated with death in hospital. Older age, longer acute kidney injury lasting time, longer acute lung injury lasting time, longer acute liver injury lasting time, and longer multiple organ dysfunction syndromes lasting time in predicting mortality in patients with infected pancreatic necrosis after surgical intervention were (0.635 [95% confidence interval (CI): 0.512–0.758], P = .040), (0.877 [95% CI: 0.788–0.965], P = .000], (0.932 [95% CI: 0.897–0.968], P = .000), (0.822 [95% CI: 0.708–0.935], P = .000), and (0.943 [95% CI: 0.887–0.998], P = .000). Due to the small number of death cases, the results of the multivariate analyses were not available.

Conclusion:

In this single-center retrospective study of 186 cases of infected pancreas necrosis, the correlative factors of death are identified. The results warranted further strategies are needed especially focusing on elder patients to prevent blood infection and to protect the functions of vital organs.
An Intensivist-Led Extracorporeal Membrane Oxygenation Program: Design, Implementation, and Outcomes of the First Five Years
Authors: Kraai Erik , Teixeira J. Pedro , Patel Ishan A. , Wray Trenton C. , Mitchell Jessica A. , George Naomi , Kamm Ashley , Henson Justin , Mirrhakimov Aibek , Guliani Sundeep , Tawil Isaac , Dettmer Todd , Marinaro Jonathan
Published: December 2022

We describe the development, implementation, and outcomes of an intensivist-led adult extracorporeal life support (ECLS) program using intensivists both to perform venovenous (V-V), venoarterial (V-A), and extracorporeal cardiopulmonary resuscitation (ECPR) cannulations, and to manage patients on ECLS throughout their ICU course. All adults supported with ECLS at the University of New Mexico Hospital (UNMH) from February 1, 2017 to December 31, 2021 were retrospectively analyzed. A total of 203 ECLS cannulations were performed in 198 patients, including 116 V-A cannulations (including 65 during ECPR) and 87 V-V cannulations (including 38 in patients with COVID-19). UNMH intensivists performed 195 cannulations, with 9 cannulation complications. Cardiothoracic surgeons performed 8 cannulations. Overall survival to hospital discharge or transfer was 46.5%. Survival was 32.3% in the ECPR group and 56% in the non-ECPR V-A group. In the V-V cohort, survival was 66.7% in the COVID-19-negative patients and 34.2% in the COVID-19-positive patients. This large series of intensivist-performed ECLS cannulations—including V-A, V-V, and ECPR modalities—demonstrates the successful implementation of a comprehensive intensivist-led ECLS program. With outcomes comparable to those in the literature, our program serves as a model for the initiation and development of ECLS programs in settings with limited access to local subspecialty cardiothoracic surgical services.
Halomonas getboli sp. nov., a halotolerant bacteria isolated from a salt flat
Authors: Yoo Yeonjae , Lee Hanbyul , Khim Jong Seong , Xu Xiaoyue , Kim Bogun , Choi In-Geol , Kim Jae-Jin
Published: December 2022

A novel Gram-stain-negative, rod-shaped, cream-coloured, motile, halotolerant bacterium, designated as YJPS3-2T, was isolated from saltern sediment of the Yellow sea in Yongyu-do, Republic of Korea. Strain YJPS3-2T grew at pH 5.0–10.0 (optimum, pH 7.0), 4–40 °C (optimum, 30 °C) and with 1–15% (w/v) NaCl (optimum 3 %). The 16S rRNA gene sequence analysis indicated that strain YJPS3-2T was closely related to those of

Halomonas halophila

F5-7T (98.75 %),

Halomonas salina

F8-11T (98.74 %),

Halomonas smyrnensis

AAD6T (98.66 %),

Halomonas organivorans

G-16.1T (98.34 %),

Halomonas koreensis

SS20T (97.98 %) and

Halomonas beimenensis

NTU-107T (96.93 %). The average nucleotide identity and digital DNA–DNA hybridization values between YJPS3-2T and related type strains were 86.9–91.6 % and 32.0–44.8 %. Strain YJPS3-2T was characterized as having Q-9 as the predominant respiratory quinone and the principal fatty acids (>10 %) were C16 : 0 (31.4 %), C19 : 0
ω8c cyclo (16.3 %), C17 : 0 cyclo (11.9 %) and C12 : 0 3-OH (10.4 %). The polar lipids consisted of phosphatidylcholine, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content of strain YJPS3-2T is 68.1mol %. Based on the polyphasic taxonomic evidence presented in this study, YJPS3-2T should be classified as representing a novel species within the genus Halmonas, for which name Halomonas getboli is proposed, with the type strain YJPS3-2T (= KCTC 92124T=KACC 22561T=JCM 35085T).
Characterization of invasive meningococcal disease case isolates in Atlantic Canada, 2014 to 2020: spatial–temporal variations of clones and predicted meningococcal B vaccine coverage
Authors: Tsang Raymond S. W. , Law Dennis K.S. , Zhou Jianwei , Haldane David , Garceau Richard , Zahariadis George , Mead Kristen , Alexander David
Published: December 2022

Introduction. Invasive meningococcal disease (IMD) caused by

Neisseria meningitidis

may show temporal and geographical changes in both the epidemiology and the characteristics of the strains involved.

Gap statement. A study that examined invasive

N. meningitidis

causing IMD in Atlantic Canada from 2009 to 2013 was published in 2014. Data from subsequent years have not been described.

Aim. This study examined the molecular epidemiology of IMD in four Atlantic Provinces of Canada as well as potential serogroup B (MenB) vaccine coverage.

Methods. Individual IMD case isolates recovered from 2014 to 2020 were analysed for serotype and serosubtype antigens as well as by whole-genome sequencing (WGS) for prediction of potential MenB vaccine coverage.

Results. Of the 56 IMD isolates, 42, 8, 5 and 1 were MenB, serogroup Y, serogroup W (MenW) and serogroup C, respectively. Geographical differences in the distribution of MenB clones revealed concentration of sequence type (ST)-269 clonal complex (cc) and ST-60 cc in Newfoundland and Labrador, while ST-41/44 cc (particularly ST-154) was predominantly found in New Brunswick and Nova Scotia. Core genome multi-locus sequence typing (cgMLST) also separated the New Brunswick and Nova Scotia ST-154 isolates into two clusters, with differences in their nhba and penA alleles. Furthermore, cgMLST also separated the ST-269 cc isolates in Atlantic Canada into the ST-1611 and the ST-269/ST-8924 clusters, with the latter showing high similarity to the ST-269 that first emerged in the Province of Quebec. Genetic Meningococcal Antigen Typing System showed that 54.8 % of MenB were predicted to be covered by the MenB vaccine Bexsero, with a further 38.1 % potentially covered by virtue of the presence of genes that encoded factor H-binding protein variant 1 proteins. Meningococcal deduced vaccine antigen reactivity predicted from WGS data showed that 95.3 % of MenB were covered by Trumenba. Four cases of IMD due to MenW ST-11 cc were also identified, with the first case found in 2018.

Conclusions. This study provided evidence concerning the dynamics of

N. meningitidis

strains causing IMD in Atlantic Canada, with both geographical and temporal differences found. MenB vaccine appeared to provide good coverage of MenB IMD, especially towards the predominant strain of ST-154.
Enterotypes of the human gut mycobiome
Authors: Lai Senying , Yan Yan , Pu Yanni , Lin Shuchun , Qiu Jian-Ge , Jiang Bing-Hua , Keller Marisa , Wang Mingyu , Bork Peer , Chen Wei-Hua , Zheng Yan , Zhao Xing-Ming
Published: December 2022

The fungal component of the human gut microbiome, also known as the mycobiome, plays a vital role in intestinal ecology and human health. Here, we identify and characterize four mycobiome enterotypes using ITS profiling of 3,363 samples from 16 cohorts across three continents, including 572 newly profiled samples from China. These enterotypes exhibit stability across populations and geographical locations and significant correlation with bacterial enterotypes. Particularly, we notice that fungal enterotypes have a strong age preference, where the enterotype dominated byCandida(i.e., fun_C_E enterotype) is enriched in the elderly population and confers an increased risk of multiple diseases associated with compromised intestinal barrier. In addition, bidirectional mediation analysis reveals that the fungi-contributed aerobic respiration pathway associated with fun_C_E enterotype might mediate the association between the compromised intestinal barrier and aging.

Teaser

As an integral part of the human gut microbiome, the fungi, which co-habit with prokaryotic microbiome in the gut, play important role in the intestinal ecology and human health. Yet, the overall structure of the human gut mycobiome and the inter-individual variation worldwide remain largely unclear.Laiet al. analyzed the fungal profiles of 3,363 samples from 16 cohorts across three continents, and identified four fungal enterotypes that exhibit stability across populations. They found that fungal enterotypes showed age preference, where aCandidadominated enterotype was enriched in the elderly population and confers an increased risk of multiple diseases and more severe compromised intestinal barrier. Furthermore, they determined one fungi-contributed aerobic respiration pathway could mediate the association between the compromised intestinal barrier and aging.
A Translational Tissue Engineering Approach to Airway Reconstruction Leveraging Decellularized Meniscus and Cartilage Progenitor Cells
Authors: Gehret Paul , Akbari Ghavimi Sohelia Ali , Dumas Alexandra , Borek Ryan C. , Aronson Matthew , Carpenter Kelsey , Jacobs Ian N. , Gottardi Riccardo
Published: December 2022

Severe subglottic stenosis develops in over 20,000 infants per year and requires laryngotracheal reconstruction (LTR) to enlarge the airway by implanting autologous cartilage from a rib graft. However, young children often lack sufficiently sized costal cartilage resulting in increased donor site morbidity and operative time, as well as an elevated risk for airway restenosis necessitating revision surgery. To overcome these limitations, we have created a first-of-its-kind scaffold based on porcine meniscal cartilage decellularization (MEND) by selectively digesting the elastin and blood vessels uniquely present in the meniscus to create microchannels that support cellular re-invasion. Here we demonstrated that MEND can be fully recellularized in 3 days with ear-derived cartilage progenitor cells (eCPCs) and reaches structural and functional maturation suitable for implant within 3 weeks of chondrogenic differentiation, a time frame compatible with clinical translation, a first in airway tissue engineering. To further this therapy toward clinical translation, we validated the eCPCs-MEND grafts in a New Zealand white rabbit LTR model. Our results demonstrated airway expansion, graft re-epitheliazation, neocartilage formation, and integration with adjacent native laryngotracheal cartilage, notably at a higher degree than the standard of care of autologous costal cartilage. No instances of adverse events of extrusion, granulation, infection, or calcification were observed in any of the 38 rabbits of our 3 months study. These results demonstrate the feasibility of our translational tissue engineering approach to laryngotracheal reconstruction and could overcome the autograft-associated limitations in pediatric patients and a decrease the risk of invasive revision surgery.
A High-resolution Haplotype-resolved Reference Panel Constructed from the China Kadoorie Biobank Study
Authors: Yu Canqing , Lan Xianmei , Tao Ye , Guo Yu , Sun Dianjianyi , Qian Puyi , Zhou Yuwen , Walters Robin , Li Linxuan , Millwood Iona , Zeng Jingyu , Pei Pei , Guo Ruidong , Du Huaidong , Yang Tao , Yang Ling , Yang Fan , Chen Yiping , Chen Fengzhen , Jiang Xiaosen , Ye Zhiqiang , Ren Fangyi , Dai Lanlan , Wei Xiaofeng , Xu Xun , Yang Huanming , Wang Jian , Chen Zhengming , Zhu Huanhuan , Lv Jun , Jin Xin , Li Liming
Published: December 2022

Precision medicine relies on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is currently not suitable for studies with very large sample sizes due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we selected 9,950 individuals from the China Kadoorie Biobank (CKB) cohort and 50 Chinese samples from the 1000 Genome Project (1KGP) for medium-depth WGS to construct a CKB reference panel. The results of imputing microarray datasets showed that the CKB panel outperformed the extended high coverage 1KGP, TOPMed, ChinaMAP, and NuyWa panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of over 100,000 CKB microarray data with the CKB panel, and the after-imputed genotype data is the hitherto largest whole genome data of the Chinese population. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the constructed CKB reference panel is of great value for imputing microarray or low-depth genotype data of Chinese population. The imputation-completed 100,000 microarray data are fundamental resources of population genetic studies for complex traits and diseases in the Chinese population.
A dedicated hypothalamic oxytocin circuit controls aversive social learning
Authors: Osakada Takuya , Yan Rongzhen , Jiang Yiwen , Wei Dongyu , Tabuchi Rina , Dai Bing , Wang Xiaohan , Zhao Gavin , Wang Clara Xi , Tsien Richard W. , Mar Adam C. , Lin Dayu
Published: December 2022

To survive and thrive in a complex social group, it is essential to not only know who to approach but more importantly who to avoid. After a single defeat, mice learn to stay away from the winning aggressor for weeks. Here, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin receptor expressing cells in the anterior subdivision of ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance learning. After defeat, aVMHvlOXTRcells drastically increase their responses to aggressor cues. This response change is functionally important as optogenetic activation of aVMHvlOXTRcells elicits time-locked social avoidance towards a benign social target whereas inactivating the cells suppresses defeat-induced social avoidance. Furthermore, OXTR in the aVMHvl is itself essential for the behavior change. Knocking out OXTR in the aVMHvl or antagonizing the receptor during defeat, but not during post-defeat social interaction, impairs defeat-induced social avoidance. aVMHvlOXTRreceives its private source of oxytocin from SOROXTcells, which are highly activated by the noxious somatosensory inputs associated with defeat. Oxytocin released from SOROXTdepolarizes aVMHvlOXTRcells and facilitates their synaptic potentiation, and hence, increases aVMHvlOXTRcell responses to aggressor cues. Ablating SOROXTcells impairs defeat-induced social avoidance learning whereas activating the cells promotes social avoidance after a subthreshold defeat experience. Altogether, our study reveals an essential role of SOROXT-aVMHvlOXTRcircuit in defeat-induced social learning and highlights the importance of brain oxytocin system in social plasticity.
Microhabitat and ontogenetic variation of thermal tolerance in complex ectotherm life cycles
Authors: Kong Jacinta D , Wu Nicholas C
Published: December 2022

Thermal tolerances, such as critical temperatures, are important indices for understanding an organism's vulnerability to changing environmental temperature. Differences in thermal tolerance over ontogeny may generate a thermal bottleneck that sets the climate vulnerability for organisms with complex life cycles. However, a species' microhabitat preference and life history can hinder our ability to assess climate change vulnerability in large-scale comparative studies as these reflect local adaptation. Here, we used phylogenetically informed, multi-level models with a global dataset of upper critical temperatures from 438 Anuran species that explicitly included microhabitat preferences and ontogenetic stage to examine variation in upper critical temperatures. We found ontogenetic trends in thermal tolerance were similar across microhabitat preferences. We then used microclimate-driven models of the heat and water budget of a thermoregulating frog to show the contribution of behavioural thermoregulation towards mitigating exposure to thermal stress. Our results suggested thermal bottlenecks are not strongly present in Anurans but instead implied strong developmental or genetic conservatism of thermal tolerance within families and ecotypes, and that behavioural thermoregulation has a strong potential for buffering frogs against extreme temperatures.
Cultural transmission, competition for prey, and the evolution of cooperative hunting
Authors: Borofsky Talia , Feldman Marcus W. , Ram Yoav
Published: December 2022

Although cooperative hunting (CH) is widespread among animals, its benefits are unclear. When rare, CH may allow predators to escape competition and access “big prey” (BP). However, a lone CH predator cannot such catch food. Cultural transmission may allow CH to spread fast enough that cooperators can find hunting partners, but competition for BP may increase. We construct a one-predator, two-prey model in which the predators either learn to hunt “small prey” (SP) alone, or learn to hunt BP cooperatively. The predators first learn vertically and then choose partners from which they learn horizontally with probabilityH. CH predators only catch the BP if their partner is cooperative. We find that without horizontal learning, CH cannot evolve when initially rare. Together, a high probability of horizontal learning and competition for the SP allow CH to evolve. However, CH can only fix in the predator population if the BP is very abundant. Furthermore, a mutant that increases horizontal learning can invade whenever CH is present but not fixed, because horizontal learning allows predators to match their strategies, avoiding the situation in which a cooperator cannot find a partner. While competition for prey is important for determining the degree of CH that evolves, it is not enough for CH to emerge and spread; horizontal cultural transmission is essential. Future models may explore factors that control how horizontal transmission influences cooperative predation, and vice versa. Lessons from our model may be useful in conservation efforts and wildlife reintroduction programs.
Estimating the transmission dynamics of Omicron in Beijing, November to December 2022
Authors: Leung Kathy , Lau Eric H. Y. , Wong Carlos K. H. , Leung Gabriel M. , Wu Joseph T.
Published: December 2022

We tracked the effective reproduction numberRtof SARS-CoV-2 Omicron BF.7 in Beijing in November – December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on November 1-11 (when the zero-covid interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on December 10-22 and self-reported to have been previously test-positive since November 1. After the announcement of “20 measures”, we estimated thatRtincreased to 3.44 (95% CrI: 2.82 – 4.14) on November 18 and the infection incidence peaked on December 11. The cumulative infection attack rate (i.e. the proportion of population who have been infected since November 1) was 43.1% (95% CrI: 25.6 – 60.9) on December 14 and 75.7% (95% CrI: 60.7 – 84.4) on December 22. Surveillance programmes should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China.
Depression and its associated factors among COVID-19 survivors in a middle income country
Authors: Moy Foong Ming , Jian Lim Eugene Ri , Hairi Noran Naqiah , Bulgiba Awang
Published: December 2022

Introduction

COVID-19 survivors who have mental health issues are more likely to have a lower quality of life, reduced work productivity, social troubles, and other health issues. However, information on the mental health of COVID-19 survivors is scarce. Therefore, we aimed to determine the COVID-19 survivors’ mental health status in the form of depression and its associated factors.

Methods

This was a cross-sectional study conducted in Malaysia, from July to September 2021, during a nationwide lockdown. Data was collected using an online questionnaire shared on social and news media. Socio-demographic variables, comorbidities, self-perception of health, information on the person’s acute condition during COVID-19 infection, symptoms and duration of symptoms post-COVID, and state of depression were gathered. The Patient Health Questionnaire 9 was used to assess depression. Factors associated with mild to severe depression were analysed using both univariable and multivariable logistic regression analyses.

Results

A total of 732 COVID-19 survivors responded to the survey. The respondents were mainly females and of younger age (in their 20s and 30s). Two-thirds perceived themselves to be in good health. One in five reported to have experienced Long COVID. Slightly less than half (47.3%) of the respondents had mild to severe depression (total PHQ-9 score of 5 -27). In the multivariable analysis, being female (aOR: 1.68; 95% CI: 1.08,2.62), of younger age (20s – aOR: 3.26; 95% CI: 1.47, 7.25; 30s – aOR: 2.08; 95% CI: 1.05, 4.15; and 40s – aOR: 2.43; 95% CI: 1.20, 4.90; compared to those in the 50s and above), being overweight/obese (aOR: 1.83; 95% CI: 1.18, 2.83), having Long COVID (aOR: 2.45; 95% CI: 1.45, 4.16) and perceiving to have poorer health (aOR: 4.54; 95% CI: 2.89, 7.13) were associated with mild to severe depression.

Conclusion

Females, younger age groups, being overweight/obese, having Long COVID and perceiving to be in poor health were factors associated with higher odds for mild to severe depression.
ASXL1mutations that cause Bohring Opitz Syndrome (BOS) or acute myeloid leukemia share epigenomic and transcriptomic signatures
Authors: Lin Isabella , Awamleh Zain , Wei Angela , Russell Bianca , Weksberg Rosanna , Arboleda Valerie A.
Published: December 2022

De novo, truncating variants ofASXL1cause two distinct disorders: Bohring-Opitz Syndrome (BOS, OMIM #605039) a rare pediatric disorder characterized by multiorgan anomalies that disrupt normal brain, heart, and bone development causing severe intellectual disability or are somatic driver mutations causing acute myeloid leukemia(AML). Despite their distinct clinical presentations, we propose thatASXL1mutations drive common epigenetic and transcriptomic dysregulation in BOS and AML. We analyzed DNA methylation (DNAm) and RNA-seq data from BOS patients (n=13) and controls (n=38) and publicly available DNAm of AML cases with (n=3) and without (n=3)ASXL1mutations from The Cancer Genome Atlas (TCGA), and RNA-seq data from AML cases (n=27) from the Beat AML cohort. Using a DNA-methylation based episignature that we previously developed for BOS, we clustered AML, BOS and normal controls together. We showed that AML samples withASXL1mutations clustered closest to individuals with BOS, whereas individuals with AML withoutASXL1mutations clustered separately. We also observe common dysregulation of the transcriptome between BOS and AML withASXL1mutations compared to controls. Our transcriptomic analysis identified 821 significantly differentially expressed genes that were shared between both data sets and 74.9% showed differential expression in the same direction. BOS patients are rare and have some reports of tumors but no clear guidelines on cancer screening protocols. This represents the first direct comparison between distinct diseases that show common epigenetic and transcriptomic effects, and potentially common drug targets for patients harboringASXL1mutations on the epigenome and transcriptome.

KEY POINTS

Acute myeloid leukemias harboring somaticASXL1driver mutations and Bohring-Opitz syndrome caused by germlineASXL1mutations share common epigenomic and transcriptomic dysregulation

A gene-centric approach can inform molecular mechanisms across distinct disease types and point towards shared targetable pathways.
Chiral and nematic phases of flexible active filaments
Authors: Dunajova Zuzana , Mateu Batirtze Prats , Radler Philipp , Lim Keesiang , Velicky Philipp , Danzl Johann Georg , Wong Richard W. , Elgeti Jens , Hannezo Edouard , Loose Martin
Published: December 2022

The emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, the tubulin-homolog FtsZ polymerizes into treadmilling filaments that further assemble into a cytoskeletal ring. Although minimalin vitroassays have shown the striking self-organization capacity of FtsZ filaments, such as dynamic chiral assemblies, how these large-scale structures emerge and relate to individual filament properties remains poorly understood. To understand this quantitatively, we combined minimal chiral active matter simulations with biochemical reconstitution experiments. Using STED and TIRF microscopy as well as high-speed AFM, we imaged the behavior of FtsZ filaments on different spatial scales. Simulations and experiments revealed that filament density and flexibility define the local and global order of the system: At intermediate densities, flexible filaments organize into chiral rings and polar bands, while an effectively nematic organization dominates for high filament densities and for mutant filaments with increased rigidity. Our predicted phase diagram captured these features quantitatively, demonstrating how filament flexibility, density and chirality cooperate with activity to give rise to a large repertoire of collective behaviors. These properties are likely important for the dynamic organization of soft chiral matter, including that of treadmilling FtsZ filaments during bacterial cell division.
Restoring glucose homeostasis with stomach-derived human insulin-secreting organoids
Authors: Huang Xiaofeng , Gu Wei , Zhang Jiaoyue , Lan Ying , Colarusso Jonathan L. , Li Sanlan , Pertl Christoph , Lu Jiaqi , Kim Hyunkee , Zhu Jian , Sévigny Jean , Zhou Qiao
Published: December 2022

Gut stem cells are accessible by biopsy and propagate robustly in culture, offering an invaluable resource for autologous cell therapies. Insulin-producing cells can be induced in mouse gut, but it has not been possible to generate abundant and durable insulin-secreting cells from human gut tissues to evaluate their potential as a cell therapy for diabetes. Here we describe a protocol to differentiate cultured human gastric stem cells (hGSCs) into pancreatic islet-like organoids containing gastric insulin-secreting (GINS) cells that resemble β-cells in molecular hallmarks and function. Sequential activation of the inducing factors NGN3 and PDX1-MAFA led hGSCs onto a novel differentiation path, including a SOX4Highendocrine and GalaninHighGINS precursor, before adopting β-cell identity, at efficiencies close to 70%. GINS organoids acquired glucose-stimulated insulin secretion in 10 days and restored glucose homeostasis for over 100 days in diabetic mice after transplantation, providing proof of concept for a new approach to treat diabetes.
Piccolino regulates the architecture of the ribbon at cochlear inner hair cell synapses
Authors: Michanski Susann , Kapoor Rohan , Steyer Anna M. , Möbius Wiebke , Früholz Iris , Ackermann Frauke , Gültas Mehmet , Garner Craig C. , Hamra F. Kent , Neef Jakob , Strenzke Nicola , Moser Tobias , Wichmann Carolin
Published: December 2022

Cochlear inner hair cells (IHCs) form specialized ribbon synapses with spiral ganglion neurons that tireless-ly transmit sound information at high rates over long time periods with extreme temporal precision. This functional specialization is essential for precise sound encoding and is attributed to a distinct molecular machinery with unique players or splice variants compared to conventional neuronal synapses. Among these is the active zone (AZ) scaffold protein piccolo/aczonin, which is represented by its short splice variant piccolino at cochlear and retinal ribbon synapses. While the function of piccolo at synapses of the central nervous system has been intensively investigated, the role of piccolino at IHC synapses remains unclear. In this study, we characterized the structure and function of IHC-synapses in piccolo gene-trap mutant rats (Pclogt/gt). We found a mild hearing deficit with elevated thresholds and reduced amplitudes of auditory brainstem responses. Ca2+channel distribution and ribbon morphology were altered in apical IHCs, while their presynaptic function seemed unchanged. We conclude that piccolino contributes to the AZ organization in IHCs and is essential for normal synaptic transmission.