bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with low antiretroviral therapy enrollment of children in the Simiyu region: A cross-sectional Creswell mixed-methods sequential explanatory design
Authors: Mageda Kihulya , Kulemba Khamis , Kapologwe Ntuli , Katalambula Leonard , Petrucka Pammla
Published: April 2023

Despite substantial antiretroviral therapy (ART) coverage in other groups with the human immunodeficiency virus (HIV) in Tanzania, there is a progressive decline in ART enrollment among HIV-infected children. This study aimed to determine the factors affecting the enrollment of children with HIV in ART and to identify an effective, sustainable intervention to address children’s ART care enrollment. To achieve this, we conducted a cross-sectional study using a mixed-method sequential explanatory design, including children with HIV aged 2 to 14 years in the Simiyu region. Stata™ and NVIVO™ software were used to perform quantitative and qualitative data analyses, respectively. In the quantitative analyses, we considered 427 children, with a mean age of 8.54 ± 3.54 years and a median age of 3 years (interquartile range: 1–6 years). The mean length of ART initiation delay was 3.71 ± 3.21 years. Additionally, independent child enrollment predictors included distance to the facility (adjusted odds ratio [AOR]: 3.31; 95% confidence interval [CI]:1.14–9.58), caregivers’ income (AOR: 0.17; 95% CI: 0.07–0.43), and fear of stigma (AOR: 3.43; 95% CI: 1.14–10.35). In qualitative analyses, 36 respondents reported that stigma, distance, and lack of HIV-positive status disclosure to their fathers were causes for low enrollment in ART. Overall, this study demonstrated that a caregiver’s income, distance to obtain HIV care services, HIV-positive status non-disclosure to the father, and fear of stigma played a significant role in children’s enrollment in HIV care. As such, HIV/acquired immunodeficiency syndrome programs would benefit from having intensive interventions to address distance, such as scaling up care and treatment centers, as well as techniques to reduce stigma in the population.
Association between obesity and osteoarthritis in the South Korean older population: A nationwide population-based study
Authors: Park Jae-Min
Published: April 2023

There are few studies on the association between obesity and radiologically-confirmed osteoarthritis (OA) in the South Korean older population. We investigated the association between obesity and radiologically-confirmed OA in a nationally-representative sample of the South Korean older population. The study population comprised 5811 participants (2530 men and 3281 women) aged ≥60 years selected from the 2010 to 2012 Korea National Health and Nutrition Examination Survey. Radiographic OA was defined as Kellgren–Lawrence grade ≥ 2 on either the knee or hip area in radiographic images. The odds ratios and 95% confidence intervals for OA were determined using multiple logistic regression analyses after adjusting for confounding factors. Overall, 7.9% and 29.6% of older men and women had OA, respectively. A U-shaped curve with the nadir in the appropriate body weight (body mass index 18.5–23 kg/m2) revealed that 9.0%, 6.8%, 8.1%, and 9.1% of older men and 24.5%, 21.6%, 27.1%, and 38.4% of older women who were underweight, normal weight, overweight, and obese, respectively, had OA. Compared with normal-weight people, the odds ratios (95% confidence intervals) for OA in obese subjects were 1.73 (1.13–2.64) and 2.76 (2.13–3.56) for older men and women, respectively, after adjusting for age, comorbidities, lifestyle behaviors, and socioeconomic status. Obesity was significantly associated with an increased risk of OA in the South Korean older population. This finding suggests that efforts to maintain appropriate body weight and reduce excessive body weight should be considered to reduce the risk of OA in older adults.
Pancreatic insulinoma misdiagnosed as atrial fibrillation: A case report from Iraq
Authors: Mahmood Aqeel Shakir , Al-Obaidi Ahmed Dheyaa , Ibrahim Mazin Judy , Al-Obaidi Mustafa Najah , Shakir Ahmed A. , Bakose Reema Yousif , Wajdi Naseem , Hashim Hashim Talib
Published: April 2023

Rationale:

Pancreatic insulinomas are the most frequent pancreatic endocrine neoplasms. They are insulin-secreting pancreatic tumors that induce extreme, recurrent, and near-fatal hypoglycemia. Insulinomas affect 1 to 4 individuals in a million of the general population and account for about 1% to 2% of all pancreatic tumors.

Patient concerns:

Recurrent episodes of sweating, tremor, weakness, confusion, palpitation, blurred vision, and fainting for 2 months and was misdiagnosed as having atrial fibrillation.

Diagnosis:

He was misdiagnosed as having atrial fibrillation to highlight the importance of atrial fibrillation as unusual mimicker of insulinoma and to encourage clinicians about the importance of early and appropriate management in such cases.

Interventions:

Endoscopic ultrasound for the pancreatic parenchyma was done, and it showed a hypoechoic homogenous mass located at the pancreatic head measuring 12 mm × 15 mm with no local vascular involvement, blue in elastography, hypervascular with Doppler study, and a normal pancreatic duct diameter.

Outcomes:

His condition was stable, and he was discharged home 2 days later.

Conclusion:

The diagnosis of insulinoma is usually difficult and late due to the extremely low incidence of the disease and the similarity of its clinical presentation to numerous other conditions, the most reported is epilepsy.
Pregnancy course and outcomes of patients with polymyositis and dermatomyositis (PM/DM) managed in a single center
Authors: Mino Rina , Shimada Hiromi , Wakiya Risa , Nakashima Shusaku , Miyagi Taichi , Sugihara Koichi , Ushio Yusuke , Mizusaki Mao , Chujo Kanako , Kameda Tomohiro , Kanenishi Kenji , Kadowaki Norimitsu , Dobashi Hiroaki
Published: April 2023

We aimed to determine the association between disease activity during pregnancy and pregnancy outcomes of women with polymyositis and dermatomyositis (PM/DM). Patients with PM/DM who were managed from pregnancy to delivery at Kagawa University Hospital from March 2006 to May 2021 were enrolled. Clinical data were retrospectively analyzed to evaluate the association between disease activity during pregnancy and pregnancy outcomes. Eight pregnancies in 5 women with PM/DM were analyzed. The mean age at conception was 28.3 ± 3.8 years, and mean disease duration was 6.3 ± 3.2 years. Four patients required an increased glucocorticoid dosage because of worsening disease activity (sustained elevation of creatine phosphokinase [CPK] concentration). Two patients who continuously received immunosuppressive drugs from conception to delivery showed no increase in disease activity and did not need increased glucocorticoid dosages. The pregnancy outcomes were 1 spontaneous abortion and 7 live births. The mean gestation length was 35.3 ± 5.2 weeks, and mean birthweight was 2297.7 ± 1041.4 g. Five adverse pregnancy outcomes (APOs) occurred (2 preterm births and 4 low birthweights); most of these cases had sustained elevation of CPK concentration and increased glucocorticoid dosages. No APOs occurred in the 2 patients who received continuous immunosuppressive medication. Continued use of pregnancy-compatible medications and control of disease activity with lower glucocorticoid dosages in pregnancies with PM/DM may be important to achieve good pregnancy outcomes.
The influencing factors of choosing future medical specialties among students in Saudi Arabia: A nationwide multicenter survey
Authors: Asiri Waddah M. Alalmaei , Shati Ayed A. , Alrowaibah Norah A. , Althumairi Rana K. , Alqahtani Ghadir M. , Mahmood Syed Esam
Published: April 2023

Choosing a future medical speciality is considered one of the most critical challenges for undergraduate students worldwide. The present study assessed the influences and factors related to medical students career choices in Saudi Arabia. The study was designed in a cross-sectional manner to collect data from all undergraduate medical students and interns in the Kingdom of Saudi Arabia for 5 months, starting from September 2021 and ending in January 2022. The questionnaire was completed by 1725 medical students and interns aged 18 to 30 with a mean age of 24.2 ± 4.6 years, and 64.6% were females. In all, 50.4% of respondents reported that they had received advice from others on their chosen speciality, and 89% of respondents indicated that they were interested in working in a specialized field after graduation. The most influencing factors for choosing medical specialities are job safety, creative ability, dealing with a variety of patients and monthly income (69.6%, 63.7%, 62.4%, 58.9%), respectively. Additionally, the study showed that gender plays a significant role (P = .001) for medical students and interns in their choice of speciality, whereas pediatrics was the top choice for female students (12%), and medicine was the most popular choice for male students (14.1%). A student’s lower grade point average, the lower average monthly income of their family, lack of working relative in the healthcare field and absence of advice about future specialities are all significant predictors for stopping specialities endeavor. Our study concluded that students career choices depend on different factors, including gender based preferences and that their specialized preferences did not change considerably prior to or after graduation. Further studies are required to analyze the factors influencing student and intern speciality preferences in their early clinical and career years.
Effectiveness of hyperbaric oxygen therapy in bone marrow edemas of the knee: A retrospective study
Authors: Ozturan Burak , Akyuerek Muhlik
Published: April 2023

Bone marrow edema (BME) is a self-limiting syndrome that can be caused by many pathological conditions. The most frequently seen symptom of BME is pain. Hyperbaric oxygen therapy (HBOT) is an available treatment. This study aims to present the clinical results of quantitatively evaluating the use of HBOT. We evaluated all BME patients 18 to 65 years old without osteoarthritis, inflammatory rheumatological disease, or malignancy diagnosed through magnetic resonance imaging. All were treated with acetylsalicylic acid (100 mg daily) and bisphosphonates (70 mg alendronate once a week) and were instructed to avoid weight-bearing activities. Some of the patients also received HBOT. We divided the patients into 2 groups: 1 group took HBOT; the other did not. We used the Wilcoxon test to compare groups. HBOT is an effective treatment option for BME. We quantitatively measured faster healing when HBOT was used for BME of the knee. There were no significant side effects.
Effects of Tai Chi on patients with moderate to severe COPD in stable phase
Authors: Luo Chengfang , Jiang Hongjuan , Li Hongwen , Chi Xiangyu
Published: April 2023

This study was designed to investigate the effects of Tai Chi training on moderate to severe Chronic obstructive pulmonary disease (COPD) in the stable phase. This was a 2-arm randomized clinical trial. A total of 226 COPD patients with moderate to severe in the stable phase were allocated to either the control group or the observation group. The observation of the frequency of acute exacerbation for both groups lasted for at least 52 weeks follow-up. Changes in lung function and symptom scores of health-related quality of life (St George’s Respiratory Questionnaire score) were also compared between the 2 groups. The accompanying anxiety and depressive symptoms of the patients were evaluated using the Self-Rating Depression Scale and Self-Rating Anxiety Scale prior to the procedure and 52 weeks later. Patients with moderate to severe COPD in China were divided into the Tai Chi group (n = 116) or control group (n = 110). After excluding 10 patients who fell off, 108 patients were enrolled in each group. Evidently, the matched group had higher exacerbation rate than the Tai Chi group (P < .05). Both groups showed no significant improvement in lung function (P > .05) but showed significant improvement in morbidity of acute exacerbation and quality of life (P < .05) compared with their former performance. Compared with regular therapy, Tai Chi also improved health-related quality of life (P < .05). The Self-Rating Anxiety Scale and Self-Rating Depression Scale scores of the 2 groups of patients after treatment and 52-week after treatment showed a notable decrease (P < .05). Overall, Tai Chi treatment was well tolerated. For moderate to severe COPD patients, regular treatment with Tai Chi can not only improve their health-related quality of life but also reduce the exacerbation rate compared with regular treatment alone. Tai Chi is recommended for COPD rehabilitation.
Patterns and Correlates of Nurse Departures From the Health Care Workforce
Authors: Medvec Barbara R. , Marriott Deanna J. , Khadr Lara , Ridge Laura J. , Lee Kathryn A. , Friese Christopher R. , Titler Marita G.
Published: April 2023

Background:

Health care executives and policymakers have raised concerns about the adequacy of the US nursing workforce to meet service demands. Workforce concerns have risen given the SARS-CoV-2 pandemic and chronically poor working conditions. There are few recent studies that directly survey nurses on their work plans to inform possible remedies.

Methods:

In March 2022, 9150 nurses with a Michigan license completed a survey on their plans to leave their current nursing position, reduce their hours, or pursue travel nursing. Another 1224 nurses who left their nursing position within the past 2 years also reported their reasons for departure. Logistic regression models with backward selection procedures estimated the effects of age, workplace concerns, and workplace factors on the intent to leave, hour reduction, pursuit of travel nursing (all within the next year), or departure from practice within the past 2 years.

Results:

Among practicing nurses surveyed, 39% intended to leave their position in the next year, 28% planned to reduce their clinical hours, and 18% planned to pursue travel nursing. Top-ranked workplace concerns among nurses were adequate staffing, patient safety, and staff safety. The majority of practicing nurses (84%) met the threshold for emotional exhaustion. Consistent factors associated with adverse job outcomes include inadequate staffing and resource adequacy, exhaustion, unfavorable practice environments, and workplace violence events. Frequent use of mandatory overtime was associated with a higher likelihood of departure from the practice in the past 2 years (Odds Ratio 1.72, 95% CI 1.40–2.11).

Conclusions:

The factors associated with adverse job outcomes among nurses—intent to leave, reduced clinical hours, travel nursing, or recent departure—consistently align with issues that predated the pandemic. Few nurses cite COVID as the primary cause for their planned or actual departure. To maintain an adequate nursing workforce in the United States, health systems should enact urgent efforts to reduce overtime use, strengthen work environments, implement anti-violence protocols, and ensure adequate staffing to meet patient care needs.
Skin Toxicity Due to Mercaptopurine in Maintenance Therapy Among Children With Acute Lymphoblastic Leukemia
Authors: Higgerson Kayeleigh , Flatt Terrie
Published: April 2023

Mercaptopurine is a crucial component in the treatment of acute lymphoblastic leukemia. It is associated with toxicities that can delay treatment. Mercaptopurine is metabolized into 6-thioguanine nucleotides and 6-methylomercaptopurine nucleotides (6MMPN). Accumulation of 6MMPN has previously been associated with hepatotoxicity, pancreatitis, and hypoglycemia. However, skin toxicity has rarely been reported. We report 5 cases of elevated 6MMPN levels associated with cutaneous manifestations.
Short-course Venetoclax With Standard Chemotherapy Is Effective in Early T-cell Precursor Acute Lymphoblastic Leukemia
Authors: Borah Pronamee , Dayal Nitin , Pathak Sangeeta , Naithani Rahul
Published: April 2023

Background:

Early T-cell precursor acute lymphoblastic leukemia (ETP ALL) is a high-risk subgroup of acute lymphoblastic leukemia characterized by unique immune phenotype and disease biology. ETP ALL cells share similarities with hematopoietic stem cells and myeloid progenitor cells. These patients have lower rates of complete remission and overall survival. High BCL2 expression is the main rationale for using venetoclax in ETP ALL.

Results:

We report the treatment outcomes of 2 patients with ETP ALL who achieved minimal residual disease negative remission with the short course of venetoclax.

Conclusions:

Combination therapy of short-course venetoclax with Berlin-Frankfurt-Meunster 95 regimen is an effective regimen for treating patients with ETP ALL.
Guide devices in the rehabilitation of interrupting mandibular bone defects: a proposal for a new classification
Authors: El Hawari Wijdane , Habib I Abdoul Majid , Bentahar Oussama
Published: April 2023

Interrupting mandibular surgical resections may lead to mandibular deviation toward the resected side. This further complicates future surgical and prosthodontics reconstructions. The rehabilitation of this mandibular deviation by the specialist in maxillofacial prosthodontics is often done by guide devices. This helps to prevent or reduce postsurgical mandibular deviation. The current literature lacks data on a standard classification of these devices despite the various clinical situations that require different rehabilitation techniques. After a deep appraisal of the current literature on this topic and many years of experience, the authors propose an overview of the indications, the types, and an original classification of these prosthetic devices. We believe this new classification will facilitate communication among practitioners, the development of treatment plans, and the comparison of outcomes among different expert centers.
Left-sided chylothorax following ipsilateral hemithoracic stab wound in a 20-year-old man: the first case report
Authors: Vakili Ojarood Mohammad , Samady Khanghah Ali
Published: April 2023

When the chyle, the liquid that is formed from the connection of the body’s lymphatic flows, leaks to the pleural space, chylothorax expression comes into existence. Traumatic types are due to penetrating wounds or iatrogenic during heavy thoracic oncology surgeries. To the best of our knowledge, we have reported the first case of left-sided chylothorax following an isolated stab wound in the fifth intercostal space of the same side treated by tube drainage and ‘nil per os’ dietary condition.
Increased comfortable gait speed is associated with improved gait biomechanics in persons with chronic stroke completing an 8-week forced-rate aerobic cycling intervention: a preliminary study
Authors: Linder Susan M. , Learman Ken , Miller Koop Mandy , Espy Debbie , Haupt Michael , Streicher Matt , Davidson Sara , Bethoux Francois , Nadler Nathan , Alberts Jay L.
Published: April 2023

Task-specific gait training is recommended to improve locomotor function post-stroke. Our objective was to determine the effects of a forced-rate aerobic exercise (FE) intervention on gait velocity and biomechanics in the absence of task-specific gait training. Individuals with chronic stroke (N = 14) underwent 24 sessions of FE, at a targeted aerobic intensity of 60-80% of their heart rate reserve. Change in comfortable walking speed in addition to spatiotemporal, kinematic, and kinetic variables were measured using 3D motion capture. Overground walking capacity was measured by the six-minute walk test (6MWT). To determine gait biomechanics associated with increased walking speed, spatiotemporal, kinematic, and kinetic variables were analyzed separately for those who met the minimal clinically important difference (MCID) for change in gait velocity compared with those who did not. Participants demonstrated a significant increase in gait velocity from 0.61 to 0.70 m/s (P = 0.004) and 6MWT distance from 272.1 to 325.1 meters (P < 0.001). Those who met the MCID for change in gait velocity demonstrated significantly greater improvements in spatiotemporal parameters (P = 0.041), ground reaction forces (P = 0.047), and power generation (P = 0.007) compared to those who did not. Improvements in gait velocity were accompanied by normalization of gait biomechanics.
Cancer Rehabilitation Veterans Affairs Extension for Community Healthcare Outcomes (VA-ECHO) Virtual Education Program – A Model for Virtual Learning in the COVID-19 Era
Authors: Qin Evelyn , Monda Jason , Mattox Elizabeth , Yantsides Konstantina , Ward Joan , Gorukanti Sre , Howard Ileana
Published: April 2023

Rehabilitation is important in the care of patients with cancer for improving function, pain, and quality of life. However, only a small number of clinicians are formally trained in cancer rehabilitation. Virtual learning environments may play a promising role in cancer rehabilitation education, especially in the coronavirus pandemic era where in-person learning is not readily available. A national, interprofessional cancer rehabilitation education program involving a monthly longitudinal webinar series and a two-day virtual bootcamp was developed through the US Department of Veterans Affairs Extension for Community Healthcare Outcomes (VA-ECHO) to improve VA clinician understanding of cancer rehabilitation and ultimately increase the availability of cancer rehabilitation services in the Veterans Health Administration (VHA). From March 2020 to July 2022, 923 individuals participated with an average of 72 participants per session and 204 participants per session in the bootcamp. Participants’ most common disciplines were physical therapy, occupational therapy, nursing, medicine (physicians), advanced practice providers, speech therapy, and pharmacy. Participants reported improved knowledge of cancer rehabilitation and anticipated that the knowledge would change their practice. Virtual education can be a useful means to educate VA-based healthcare professionals about cancer rehabilitation and improve access to rehabilitation services for Veterans with cancer.
Effects of a Pragmatic Home-based Exercise Program Concurrent With Neoadjuvant Therapy on Physical Function of Patients With Pancreatic Cancer
Authors: Ngo-Huang An T. , Parker Nathan H. , Xiao Lianchun , Schadler Keri L. , Petzel Maria Q.B. , Prakash Laura R. , Kim Michael P. , Tzeng Ching-Wei D. , Lee Jeffrey E. , Ikoma Naruhiko , Wolff Robert A. , Javle Milind M. , Koay Eugene J. , Pant Shubham D. , Folloder Justin P. , Wang Xuemei , Cotto Alicia M. , Ju Ye Rang , Garg Naveen , Wang Huamin , Bruera Eduardo D. , Basen-Engquist Karen M. , Katz Matthew H.G.
Published: April 2023

Objective:

To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer.

Background:

We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer.

Methods:

In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was a 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included additional physical function tests, health-related quality of life, and clinical outcomes.

Results:

One hundred fifty-one patients participated. Objectively measured weekly activity (151.6±135.0 and 161.8±123.1 min in Arm A and B, respectively, P=0.5) and self-reported weekly moderate-to-strenuous physical activity (107.4±160.4 and 130.9±162.9 min in Arm A and Arm B, respectively, P=0.47) were similar, but weekly strength training sessions increased more in Arm B (by 1.8±1.8 vs 0.1±2.4 sessions, P<0.001). 6MWD improved in both Arm A (mean change 17.8±56.7 m, P=0.02) and Arm B (28.3±68.2 m, P=0.002). Quality of life and clinical outcomes did not significantly differ between arms. Pooling patients in both study groups, exercise, and physical activity was favorably associated with physical performance and clinical outcomes.

Conclusions:

In this randomized trial of prescribed exercise versus enhanced usual care during neoadjuvant therapy for pancreatic cancer, a high volume of physical activity and increased exercise capacity were observed in both arms, highlighting the importance of activity among patients preparing for surgery.
The Neuroanatomy of Poststroke Subjective Sensory Hypersensitivity
Authors: Thielen Hella , Tuts Nora , Lafosse Christophe , Gillebert Céline Raymond
Published: April 2023

Background:

Although subjective sensory hypersensitivity is prevalent after stroke, it is rarely recognized by health care providers, and its neural mechanisms are largely unknown.

Objective:

To investigate the neuroanatomy of poststroke subjective sensory hypersensitivity as well as the sensory modalities in which subjective sensory hypersensitivity can occur by conducting both a systematic literature review and a multiple case study of patients with subjective sensory hypersensitivity.

Method:

For the systematic review, we searched three databases (Web of Science, PubMed, and Scopus) for empirical articles discussing the neuroanatomy of poststroke subjective sensory hypersensitivity in humans. We assessed the methodological quality of the included studies using the case reports critical appraisal tool and summarized the results using a qualitative synthesis. For the multiple case study, we administered a patient-friendly sensory sensitivity questionnaire to three individuals with a subacute right-hemispheric stroke and a matched control group and delineated brain lesions on a clinical brain scan.

Results:

Our systematic literature search resulted in four studies (describing eight stroke patients), all of which linked poststroke subjective sensory hypersensitivity to insular lesions. The results of our multiple case study indicated that all three stroke patients reported an atypically high sensitivity to different sensory modalities. These patients’ lesions overlapped with the right anterior insula, the claustrum, and the Rolandic operculum.

Conclusion:

Both our systematic literature review and our multiple case study provide preliminary evidence for a role of the insula in poststroke subjective sensory hypersensitivity and suggest that poststroke subjective sensory hypersensitivity can occur in different sensory modalities.
THAPBI PICT - a fast, cautious, and accurate metabarcoding analysis pipeline
Authors: Cock Peter J. A. , Cooke David E. L. , Thorpe Peter , Pritchard Leighton
Published: April 2023

THAPBI PICT is an open source software pipeline for metabarcoding analysis with multiplexed Illumina paired-end reads, including where different amplicons are sequenced together. We demonstrate using worked examples with our own and public data sets how, with appropriate primer settings and a custom database, THAPBI PICT can be applied to other amplicons and organisms, and used for reanalysis of existing datasets. The core dataflow of the implementation is (i) data reduction to unique marker sequences, often called amplicon sequence variants (ASVs), (ii) dynamic thresholds for discarding low abundance sequences to remove noise and artifacts (rather than error correction by default), before (iii) classification using a curated reference database. The default classifier assigns a label to each query sequence based on a database match that is either perfect, or a single base pair edit away (substitution, deletion or insertion). Abundance thresholds for inclusion can be set by the user or automatically using per-batch negative or synthetic control samples. Output is designed for practical interpretation by nonspecialists and includes a read report (ASVs with classification and counts per sample), sample report (samples with counts per species classification), and a topological graph of ASVs as nodes with short edit distances as edges. Source code available fromhttps://github.com/peterjc/thapbi-pict/withdocumentation including installation instructions.
Comparative Phylogenomics and Phylotranscriptomics Provide Insights into the Genetic Complexity of Nitrogen Fixing Root Nodule Symbiosis
Authors: Zhang Yu , Fu Yuan , Xian Wenfei , Li Xiuli , Feng Yong , Bu Fengjiao , Shi Yan , Chen Shiyu , van Velzen Robin , Berry Alison M. , Salgado Marco G. , Liu Hui , Yi Tingshuang , Fournier Pascale , Alloisio Nicole , Pujic Petar , Boubakri Hasna , Schranz M. Eric , Delaux Pierre-Marc , Wong Gane Ka-shu , Hocher Valerie , Svistoonoff Sergio , Gherbi Hassen , Wang Ertao , Kohlen Wouter , Wall Luis G. , Parniske Martin , Pawlowski Katharina , Philippe Normand , Doyle Jeffrey J. , Cheng Shifeng
Published: April 2023

Plant root nodule symbiosis (RNS) with mutualistic nitrogen-fixing bacteria is restricted to a single clade of angiosperms, the Nitrogen-Fixing Nodulation Clade (NFNC), and is best understood in the legume family. It is widely accepted that nodulation originated through the assembly of modules recruited from existing functions, such as mycorrhizal symbiosis, polar growth, and lateral root development. Because nodulating species are scattered within the NFNC, the number of times nodulation has evolved or has been lost has been a matter of considerable speculation. This interesting evolutionary question has practical implications concerning the ease with which nodulation might be engineered in non-nodulating crop plants. Nodulating species share many commonalities, due either to divergence from a common ancestor over 100 million years ago or to convergence or deep homology following independent origins over that same time period. In either case, comparative analyses of diverse nodulation syndromes can provide insights into constraints on nodulation—what must be acquired or cannot be lost for a functional symbiosis—and what the latitude is for variation in the symbiosis. However, much remains to be learned about nodulation, especially outside of legumes. Here we present new information across the spectrum of nodulating groups. We find no evidence for convergence at the level of amino acid residues or gene family expansion across the NFNC. Our phylogenomic analyses further emphasize the uniqueness of the transcription factor, NIN, as a master regulator of nodulation, and identify key mutations affecting its function across the NFNC. We find that nodulation genes are over-represented among orthologous gene groups (OGs) present in the NFNC common ancestor, but that lineage-specific OGs play major roles in nodulation. We identified over 900,000 conserved noncoding elements (CNEs), of which over 300,000 were unique to NFNC species. A significant proportion of these are associated with nodulation-related genes and thus are candidates for transcriptional regulators.
DrBERT: A Robust Pre-trained Model in French for Biomedical and Clinical domains
Authors: Labrak Yanis , Bazoge Adrien , Dufour Richard , Rouvier Mickael , Morin Emmanuel , Daille Béatrice , Gourraud Pierre-Antoine
Published: April 2023

In recent years, pre-trained language models (PLMs) achieve the best performance on a wide range of natural language processing (NLP) tasks. While the first models were trained on general domain data, specialized ones have emerged to more effectively treat specific domains. In this paper, we propose an original study of PLMs in the medical domain on French language. We compare, for the first time, the performance of PLMs trained on both public data from the web and private data from healthcare establishments. We also evaluate different learning strategies on a set of biomedical tasks. In particular, we show that we can take advantage of already existing biomedical PLMs in a foreign language by further pre-train it on our targeted data. Finally, we release the first specialized PLMs for the biomedical field in French, called DrBERT, as well as the largest corpus of medical data under free license on which these models are trained.
An acute microglial metabolic response controls metabolism and improves memory
Authors: Drougard Anne , Ma Eric H , Wegert Vanessa , Sheldon Ryan , Panzeri Ilaria , Vatsa Naman , Apostle Stefanos , Fagnocchi Luca , Schaf Judith , Gossens Klaus , Völker Josephine , Pang Shengru , Bremser Anna , Dror Erez , Giacona Francesca , Sagar Sagar , Henderson Michae X , Prinz Marco , Jones Russell G , Pospisilik John Andrew
Published: April 2023

Chronic high-fat feeding triggers chronic metabolic dysfunction including obesity, insulin resistance, and diabetes. How high-fat intake first triggers these pathophysiological states remains unknown. Here, we identify an acute microglial metabolic response that rapidly translates intake of high-fat diet (HFD) to a surprisingly beneficial effect on metabolism and spatial / learning memory. High-fat intake rapidly increases palmitate levels in cerebrospinal fluid and triggers a wave of microglial metabolic activation characterized by mitochondrial membrane activation and fission as well as metabolic skewing towards aerobic glycolysis. These effects are detectable throughout the brain and can be detected within as little as 12 hours of HFD exposure. In vivo, microglial ablation and conditional DRP1 deletion show that the microglial metabolic response is necessary for the acute effects of HFD. 13C-tracing experiments reveal that in addition to processing via β-oxidation, microglia shunt a substantial fraction of palmitate towards anaplerosis and re-release of bioenergetic carbons into the extracellular milieu in the form of lactate, glutamate, succinate, and intriguingly, the neuro-protective metabolite itaconate. Together, these data identify microglia as a critical nutrient regulatory node in the brain, metabolizing away harmful fatty acids and releasing the same carbons as alternate bioenergetic and protective substrates for surrounding cells. The data identify a surprisingly beneficial effect of short-term HFD on learning and memory.
Protein language model powers accurate and fast sequence search for remote homology
Authors: Liu Wei , Wang Ziye , You Ronghui , Xie Chenghan , Wei Hong , Xiong Yi , Yang Jianyi , Zhu Shanfeng
Published: April 2023

Homologous protein search is one of the most commonly used methods for protein annotation and analysis. Compared to structure search, detecting distant evolutionary relationships from sequences alone remains challenging. Here we propose PLMSearch (ProteinLanguageModel), a homologous protein search method with only sequences as input. With deep representations from a pre-trained protein language model to predict similarity, PLMSearch can capture the remote homology information hidden behind the sequences. Extensive experimental results show that PLMSearch can search millions of query-target protein pairs in seconds like MMseqs2 while increasing the sensitivity by more than threefold, and is comparable to state-of-the-art structure search methods. In particular, unlike traditional sequence search methods, PLMSearch can recall most remote homology pairs with low sequence similarity but sharing similar structures. PLMSearch is freely available athttps://dmiip.sjtu.edu.cn/PLMSearch.
Elevated glycolytic metabolism of monocytes limits the generation of HIF-1α-driven migratory dendritic cells in tuberculosis
Authors: Maio Mariano , Barros Joaquina , Joly Marine , Vahlas Zoi , Franco José Luis Marín , Genoula Melanie , Monard Sarah , Vecchione María Belén , Fuentes Federico , Polo Virginia Gonzalez , Quiroga María Florencia , Vermeulen Mónica , Manh Thien-Phong Vu , Argüello Rafael J , Inwentarz Sandra , Musella Rosa , Ciallella Lorena , Montaner Pablo González , Palmero Domingo , Villarino Geanncarlo Lugo , Sasiain María del Carmen , Neyrolles Olivier , Verollet Christel , Balboa Luciana
Published: April 2023

During tuberculosis, migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid development of protective T-cell mediated immunity. However, the mechanisms involved in the delayed migration of DCs during tuberculosis (TB) are still poorly defined. Here, we found that infection of DCs withMycobacterium tuberculosis(Mtb) triggers HIF-1α-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the lactate dehydrogenase (LDH) inhibitor oxamate and the HIF-1α inhibitor PX-478 abrogated Mtb-induced DC migrationin vitroto the lymphoid tissue-specific chemokine CCL21, andin vivoto lymph nodes in mice. Strikingly, we found that although monocytes from TB patients are inherently biased toward glycolysis metabolism, they differentiate into poorly glycolytic and poorly migratory DCs, compared with healthy subjects. Taken together, these data suggest that because of their preexisting glycolytic state, circulating monocytes from TB patients are refractory to differentiation into migratory DCs, which may explain the delayed migration of these cells during the disease and opens avenues for host-directed therapies for TB.

Graphical Abstract
Conditional Generative Learning for Medical Image Imputation
Authors: Raad Ragheb , Ray Deep , Varghese Bino , Hwang Darryl , Gill Inderbir , Duddalwar Vinay , Oberai Assad A.
Published: April 2023

Image imputation refers to the task of generating a type of medical image given images of another type. This task becomes challenging when the difference between the available images, and the image to be imputed is large. In this manuscript, one such application, derived from the dynamic contrast enhanced computed tomography (CECT) imaging of the kidneys, is considered: given an incomplete sequence of three CECT images, we are required to the impute the missing image. This task is posed as one of probabilistic inference and a generative algorithm to generate samples of the imputed image, conditioned on the available images, is developed, trained, and tested. The output of this algorithm is the “best guess” of the imputed image, and a pixel-wise image of variance in the imputation. It is demonstrated that this best guess is more accurate than those generated by other, deterministic deep-learning based algorithms, including ones which utilize additional information and more complex loss terms. It is also shown the pixel-wise variance image, which quantifies the confidence in the reconstruction, can be used to determine whether the result of the imputation meets a specified accuracy threshold and is therefore appropriate for a downstream task.
Aged Breast Matrix Bound Vesicles Promote Breast Cancer Invasiveness
Authors: Yang Jun , Bahcecioglu Gokhan , Ronan George , Zorlutuna Pinar
Published: April 2023

Aging is one of the inherent risk factors for breast cancer. Although the influence of age-related cellular alterations on breast cancer development has been extensively explored, little is known about the alterations in the aging breast tissue microenvironment, specifically the extracellular matrix (ECM). Here, for the first time in literature, we have identified tissue resident matrix bound vesicles (MBVs) within the healthy mouse breast ECM, investigated and compared their characteristics in young and aged healthy breast tissues, and studied the effects of these MBVs on normal (KTB21) and cancerous (MDA-MB-231) human mammary epithelial cells with respect to the tissue age that they are extracted from. Using vesicle labeling technology, we were able to visualize cellular uptake of the MBVs directly from the native decellularized tissue sections, showing that these MBVs have regulatory roles in the tissue microenvironment. We mimicked the ECM by embedding the MBVs in collagen gels, and showed that MBVs could be taken up by the cells. The miRNA and cytokine profiling showed that MBVs shifted towards a more tumorigenic and invasive phenotype with age, as evidenced by the more pronounced presence of cancer-associated cytokines, and higher expression levels of oncomiRs miR-10b, miR-30e, and miR-210 in MBVs isolated from aged mice. When treated with MBVs or these upregulated factors, KTB21 and MDA-MB-231 cells showed significantly higher motility and invasion compared to untreated controls. Treatment of cells with a cocktail of miRNAs (miR-10b, miR-30e, and miR-210) or with the agonist of adiponectin (AdipoRon), which both were enriched in the aged MBVs, recapitulated the effect of aged MBVs on cells. This study shows for the first time that the MBVs have a regulatory role in the tissue microenvironment and that the MBV contents change towards cancer-promoting upon aging. Studying the effects of MBVs and their cargos on cellular behavior could lead to a better understanding of the critical roles of MBVs played in breast cancer progression and metastasis.
Lessons from relatives: C4 photosynthesis enhances CO2assimilation during the low-light phase of fluctuations
Authors: Arce Cubas Lucίa , Rodrigues Gabriel Sales Cristina , Vath Richard L. , Bernardo Emmanuel L. , Burnett Angela C. , Kromdijk Johannes
Published: April 2023

Despite the global importance of species with C4photosynthesis, there is a lack of consensus regarding C4performance under fluctuating light. Contrasting hypotheses and experimental evidence suggest that C4photosynthesis is either less, or more efficient in fixing carbon under fluctuating light than the ancestral C3form. Two main issues were identified that may underly the lack of consensus: neglect of evolutionary distance between selected C3and C4species and use of contrasting fluctuating light treatments. To circumvent these issues, we compared photosynthetic responses to fluctuating light across three independent phylogenetically controlled comparisons between C3and C4species fromAlloteropsis,Flaveria, andCleomegenera under 21% and 2% O2. Leaves were subjected to repetitive stepwise changes in light intensity (800 and 100 µmol m-2s-1PFD) with three contrasting durations: 6, 30 and 300 seconds. These experiments reconcile the opposing results found across previous studies showing that 1) stimulation of CO2assimilation in C4species during the low light phase was both stronger and more sustained than in C3species; 2) CO2assimilation patterns during the high light phase were genus-specific rather than impacted by photosynthetic pathway; and 3) the duration of each light step in the fluctuation regime can strongly influence experimental outcomes.

One sentence significance statement

Comparing photosynthesis in three pairs of closely related C3and C4species across three fluctuating light regimes showed that C4photosynthesis has a systematic advantage under the low light phase not related to suppression of photorespiration, while the comparative efficiency under the high light phase was not determined by photosynthetic pathway.
Qualitatively different delay-dependent working memory distortions in people with schizophrenia and healthy control subjects
Authors: Bansal Sonia , Bae Gi-Yeul , Robinson Benjamin M , Dutterer Jenna , Hahn Britta , Luck Steven J , Gold James M
Published: April 2023

Background

Impairments in working memory(WM) have been well-documented in people with schizophrenia(PSZ). However, thesequantitativeWM impairments can often be explained by nonspecific factors, such as impaired goal maintenance. Here, we used a spatial orientation delayed-response task to explore aqualitativedifference in WM dynamics between PSZ and healthy control subjects(HCS). Specifically, we took advantage of the discovery that WM representations may drift either toward or away from previous-trial targets(serial dependence). We tested the hypothesis that WM representations drift toward the previous-trial target in HCS but away from the previous-trial target in PSZ.

Methods

We assessed serial dependence in PSZ(N=31) and HCS(N=25), using orientation as the to-be-remembered feature and memory delays from 0 to 8s. Participants were asked to remember the orientation of a teardrop-shaped object and reproduce the orientation after a varying delay period.

Results

Consistent with prior studies, we found that current-trial memory representations were less precise in PSZ than in HCS. We also found that WM for the current-trial orientation driftedtowardthe previous-trial orientation in HCS(representational attraction) but driftedawayfrom the previous-trial orientation in PSZ(representational repulsion).

Conclusions

These results demonstrate a qualitative difference in WM dynamics between PSZ and HCS that cannot easily be explained by nuisance factors such as reduced effort. Most computational neuroscience models also fail to explain these results, because they maintain information solely by means of sustained neural firing, which does not extend across trials. The results suggest a fundamental difference between PSZ and HCS in longer-term memory mechanisms that persist across trials, such as short-term potentiation and neuronal adaptation.
N-cadherin dynamically regulates pediatric glioma cell migration in complex environments
Authors: Kim Dayoung , Olson James M , Cooper Jonathan A
Published: April 2023

Pediatric high-grade gliomas are highly invasive and essentially incurable. Glioma cells migrate between neurons and glia, along axon tracts, and through extracellular matrix surrounding blood vessels and underlying the pia. Mechanisms that allow adaptation to such complex environments are poorly understood. N-cadherin is highly expressed in pediatric gliomas and associated with shorter survival. We found that inter-cellular homotypic N-cadherin interactions differentially regulate glioma migration according to the microenvironment, stimulating migration on cultured neurons or astrocytes but inhibiting invasion into reconstituted or astrocyte-deposited extracellular matrix. N-cadherin localizes to filamentous connections between migrating leader cells but to epithelial-like junctions between followers. Leader cells have more surface and recycling N-cadherin, increased YAP1/TAZ signaling, and increased proliferation relative to followers. YAP1/TAZ signaling is dynamically regulated as leaders and followers change position, leading to altered N-cadherin levels and organization. Together, the results suggest that pediatric glioma cells adapt to different microenvironments by regulating N-cadherin dynamics and cell-cell contacts.

Pediatric gliomas invade the brain by migrating between nerve cells or exploiting extracellular matrix along blood vessels. This research reveals cross-talk between YAP1/TAZ signaling and N-cadherin that regulates leader-follower cell phenotypes and migration efficiency in neural and extracellular matrix environments.