bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of pulmonary adenoid cystic carcinoma using multimodal ultrasound imaging technology: A case report
Authors: Shi Hong , Qiu Wei , Yang Ping , Zhang Yaping , Huang Tingyu , Mei Jinyuan , Yin Xinrui , Yang Yanhui
Published: January 2025

Rationale:

Pulmonary adenoid cystic carcinoma (PACC) is an exceedingly uncommon malignant tumor originating from salivary glands.

Patient concerns:

We present a case of primary PACC with multiple lung metastases in a 48-year-old male patient.

Diagnosis:

Diagnosis involved grayscale ultrasound, shear wave elastography, contrast-enhanced ultrasound, and ultrasound-guided percutaneous lung biopsy, all conducted in a one-stop manner, and confirmed by pathological examination.

Interventions:

Treatment was recommended after the diagnosis was confirmed, but was not accepted.

Outcomes:

With telephone follow-up, the patient survived.

Lessons:

PACC is an exceedingly uncommon malignant tumor originating from salivary glands. Compared to other cases, this case highlights the potential of multimodal ultrasound imaging for diagnosing lung tumors.
PD-L1 and ALK expressions in stages III and IV colorectal cancer and their correlation with clinicopathological features
Authors: Jang Kyu Yun , Kim Kyoung Min , Ha Gi Won , Lee Min Ro , Park Ho Sung , Chung Myoung Ja , Moon Woo Sung , Ahn Ae Ri
Published: January 2025

Colorectal cancer (CRC) is a type of cancer with a high recurrence rate. Studies are in the progress to identify effective treatments for CRC patients. We aimed to compare the expression of programmed death-ligand 1 (PD-L1) and anaplastic lymphoma kinase (ALK) in stages III and IV CRC patients and evaluate the clinicopathological significance associated with their expression. A total of 169 stages III and IV CRC specimens was tested for ALK (D5F3) and PD-L1 (SP142 and SP263) expression using immunohistochemistry on formalin-fixed paraffin-embedded specimens. Clinicopathological characteristics were obtained through a review of the medical records and hematoxylin and eosin slides. Expression of PD-L1 SP142 and PD-L1 SP263 was detected in 17.8% and 28.4% of CRC patients, respectively. ALK D5F3 expression was detected in 4 cases. PD-L1 SP142 expression was significantly correlated with tumor site and serum carcinoembryonic antigen (CEA) level. PD-L1 SP263 expression was associated with serum tumor marker level and tumor-infiltrating lymphocytes. In univariate analysis, PD-L1 expression was correlated with shorter survival in CRC patients. PD-L1 SP263 expression was an independent indicator of shorter survival in multivariate analysis. PD-L1 expression was associated with poor prognostic factors, including shorter survival. Further investigation is needed to understand the mechanisms of the association between PD-L1 expression and unfavorable CRC prognosis.
Using Health Belief Model to explain the factors associated with postnatal services utilization among post-delivery mothers in Zanzibar: A cross-sectional study
Authors: Salehe Faudhia A. , Omari Rehema B. , Moshi Fabiola V. , Kibusi Stephen M.
Published: January 2025

Postnatal period is the crucial period for the survival of mothers and neonates. Utilization of postnatal services has been linked with reduction of maternal and neonatal morbidity and mortality. This study used the Health Belief Model to explain factors that influence postnatal services utilization among post-delivery women in Zanzibar. A community-based cross-sectional study design was employed whereas a total of 395 post-delivery women were randomly selected. The study used the Health Belief components to derive operational variables to explain postnatal services utilization. Structured questionnaires and documentary reviews were used to collect data and analyzed using Statistical Package for Social Sciences Version 20. Binary logistic regression analysis was used to establish factors associated with postnatal utilization. The result revealed that only 115 (29.1%) used postnatal services in Zanzibar. After adjusting the confounders (education level, parity, place of delivery, mode of delivery, and maternal complications), variables of the Health Belief Model which showed a significant relationship were perceived benefit AOR = 10.212 at 95% CI = 2.509–41.567, P = .001 and cues of action AOR = 1.958 at 95% CI = 1.05–3.648, P = .034. Other variables of the Health Belief Model showed increased odds (perceived barriers AOR = 1.748 at 95% CI = 0.81–3.771 and perceived susceptibility AOR = 1.795 CI = 0.561–5.74), but they were not statistically significant. Most of postnatal mothers did not utilize postnatal services during the first month post-delivery. Sensitization campaigns such as educational campaigns are recommended to raise the awareness of postnatal women on the benefits of postnatal checkups within the first month of childbirth and hence improve the utilization.
Exploring potential treatment opportunities in a head and neck tumor patient with AdCC: A novel germline ERCC2 mutation case report
Authors: Liu Yuanhao , Han Tiantian , Guo Didi , Chen Dongsheng , Li Yunqian
Published: January 2025

Rationale:

Adenoid cystic carcinoma (AdCC) is an invasive head and neck malignancy characterized by unpredictable growth, extensive perineural invasion, a high rates of metastasis, and poor survival rates. Genetic alterations, including MYB-NFIB and MYBL1-NFIB fusions, and mutations within the Notch signaling and DNA damage repair pathways, have been identified.

Patient concerns:

A 58-year-old female presented with a space-occupying lesion of the anterior cranial fossa floor during a physical examination and sought further consultation in July 2022.

In our case, a 58-year-old woman was incidentally found to have an anterior cranial fossa lesion during a routine physical examination, which was subsequently confirmed as AdCC following postoperative immunohistochemistry.

Diagnoses:

Based on these imaging and histopathological findings, a diagnosis of AdCC was established. Integrating the genetic test results, the case was diagnosed as MYB or MYBL1 fusion-negative AdCC. This case report highlights a rare molecular signature of ERCC2 and BRCA2 inactivation in AdCC, in the absence of MYB or MYBL1 fusions.

Interventions:

The patient underwent postoperative radiotherapy (RT) to the primary site approximately 2.5 months postsurgery. The concurrent presence of germline ERCC2 and somatic BRCA2 mutations offers novel insights into potential treatment strategies for this rare malignancy.

Outcomes:

To date, no recurrence has been observed during follow-up.

Lessons:

We found a novel germline ERCC2 mutation and somatic BRCA2 mutation in a patient with AdCC. Our findings expand the molecular landscape of rare MYB or MYBL1 fusion-negative AdCC patients and provide a potential therapeutic strategy for this rare head and neck tumor.
Rare “ileum–ileum–colon type” adult intussusception caused by Meckel’s diverticulum inversion: A case report
Authors: Mao Yi-Hu , Huang Li-Bin , Jia Qi , Li Shu-Jun , Zeng Qian , Yang Jian , Yang Cai-Jun , Pu Qi , Liu Xue-Ping
Published: January 2025

Rationale:

Ileum–ileum–colon intussusception constitutes a small proportion of the classification of intussusception. Both adult intussusception and Meckel’s diverticulum are rare clinical entities, with few reports documenting Meckel’s diverticulum inversion leading to ileum–ileum–colon intussusception in adults.

Patient concerns:

A 33-year-old Chinese male presented with intermittent abdominal pain persisting for 1 month, that had intensified over the preceding day.

Diagnoses:

Abdominal computed tomography revealed intussusception, suspected to be secondary to a small intestinal lipoma.

Interventions:

Emergency laparotomy was performed, during which the ileum, located approximately 70 cm from the ileocecal region, was found to be invaginated into the terminal ileum and subsequently into the ascending colon, reaching the hepatic flexure. An inverted Meckel’s diverticulum was at the forefront of the intussusception. Surgical resection of the diverticulum, terminal ileum, and cecum was performed, followed by an end-to-side anastomosis of the ileum and colon.

Outcomes:

The patient was discharged on postoperative day 7 without complications. During a 1-month follow-up, the patient reported no discomfort and exhibited normal bowel movements.

Lessons:

Adult intussusception of the “ileum–ileum–colon type” resulting from inverted Meckel’s diverticulum is exceedingly rare and poses challenges for preoperative diagnosis. Prompt surgical intervention can lead to favorable outcomes in patients. During surgery, the initial step should involve attempting reduction of the intussusception while ensuring that the intestine is preserved as much as possible to maintain intestinal function.
Carotid femoral pulse wave velocity and serum galectin-3 level significantly increases in patients with acromegaly
Authors: Ozturk Huseyin Ali , Gulumsek Erdinc , Arici Fatih Necip , Alisan İrfan , Dincer Cahit , Ozturk Dilan Damla , Cakir Pekoz Burcak , Sumbul Hilmi Erdem
Published: January 2025

Insulin-like growth factor-1 (IGF-1) and growth hormone release is elevated in acromegaly, a chronic condition. Our objective was to study the correlation between carotid femoral pulse wave velocity (CF-PWV) and galectin-3 level in acromegaly patients. This protein is believed to alter in response to early inflammation and atherosclerosis. Our study was planned as a prospective, single-center cross-sectional study. Our study comprised 40 healthy controls and 40 newly diagnosed acromegaly patients ranging in age from 18 to 65 years old at Adana City Training and Research Hospital. The patients’ IGF-1, growth hormone, hemogram, and biochemistry values were assessed. Human galectin-3 kits and the Enzyme-Linked Immunosorbent Assay were used to measure the amount of galectin-3. Patients underwent CF-PWV assessments with the use of Doppler ultrasonography and concurrent electrocardiography. Our investigation indicated that acromegaly patients had greater levels of the fibrosis and inflammation indicator galectin-3 as well as the gold standard indication of arterial stiffness, CF-PWV. We observed a link between blood galectin-3 level and both IGF-1 level and CF-PWV measures in the correlation analysis. Galectin-3 has the potential to be a novel biomarker for the diagnosis and prognosis of cardiovascular disease in acromegaly patients, as well as a therapeutic target for the development of this disease.
A giant spinal schwannoma at the C1-C2 level: A case report
Authors: Wu Xiaodong , Li Dazhi , Zhang Lu , Li Yanming
Published: January 2025

Rationale:

Giant spinal schwannomas located at the C1-C2 level pose significant surgical challenges because of their proximity to the brainstem, cervical spinal cord, and vertebral arteries. This case provides insight into the surgical management of giant spinal schwannomas at the C1-C2 level.

Patient Concerns:

A 40-year-old female presented with a 2-year history of progressive limb numbness, weakness, and gait instability. She reported a sensation of stepping on cotton and tightness in the chest and abdomen with worsening symptoms over time.

Diagnoses:

Physical examination revealed limited cervical spine movement, increased muscle tone in the limbs, and Hoffmann and Babinski signs. Imaging, including CT, CTA and MRI, identified a large schwannoma at the C1-C2 level, with compression of the spinal cord and proximity to the vertebral artery.

Interventions:

The patient underwent surgical excision of the tumor using full laminectomy approach under intravenous anesthesia.

Outcomes:

The surgery was successfully completed, and the patient’s neurological symptoms, including numbness and weakness, were significantly relieved.

Conclusion:

Strict enucleation within the capsule can effectively protect the vertebral artery and nearby nerves. When functional nerve roots or the spinal cord are involved, leaving the residual capsule may be safer than risking permanent deficits.
Development of and Testing Novel Questionnaires Assessing Palliative Care-Related Knowledge, Attitudes, and Confidence Among Home Healthcare Clinicians, Patients, and Caregivers
Authors: Chastain Ashley M. , Shang Jingjing , Murali Komal P. , King Lori , Ogunlusi Charity , Zhao Suning , Kang Jung A. , Zhao Yihong , Dualeh Khadra , McDonald Margaret V.
Published: January 2025

Palliative care improves the quality of life for seriously ill patients, but misconceptions and knowledge gaps hinder its implementation in home healthcare (HHC). This study developed and pilot-tested HHC-specific questionnaires to measure palliative care knowledge, attitudes, and confidence (PC-KAC) among clinicians, patients, and caregivers. Using literature reviews, expert input, and cognitive interviews, the questionnaires were refined to ensure clarity, practical relevance, and content validity. Pilot testing revealed widespread confusion about palliative care, with patients and caregivers often conflating it with hospice care and holding misconceptions about opioid use for pain and symptom management. While clinicians demonstrated adequate knowledge, gaps in pain management and confidence in handling emergencies were evident. These findings highlight the need for targeted education and training to integrate palliative care effectively into HHC, improving patient outcomes and supporting interdisciplinary collaboration.
Deep Vein Thrombosis
Authors: Mager Diana R.
Published: January 2025

Deep vein thrombosis (DVT) is a commonly occurring problem-causing tissue damage, pain, immobility, and even death. This article describes the risk factors and pathophysiology associated with DVT; related signs, symptoms, and complications; diagnosing and treating DVT; and the role of the home care clinician when a patient suffers from this potentiallly debilitating and life-threatening condition.
Promoting Physical Activity in People With Parkinson’s Disease Through a Smartphone App: A Pilot Study
Authors: Schootemeijer Sabine , de Vries Nienke M. , Darweesh Sirwan K.L. , Ascherio Alberto , Schwarzschild Michael A. , Macklin Eric A. , Bloem Bastiaan R.
Published: January 2025

Background and Purpose:

Physical activity has beneficial symptomatic effects for people with Parkinson’s disease (PD), but increasing—and sustaining—a physically active lifestyle remains challenging. We investigated the feasibility (ability to increase step counts) and usability of a behavioral intervention using a motivational smartphone application to remotely increase physical activity in PD.

Methods:

We performed a 4-week, double-blind pilot trial. Thirty people with PD who were able to walk independently and did not take more than 7000 steps at baseline were randomized to minimal, moderate, or large increases in step counts. Step counts were continuously collected with the participants’ own smartphones. Usability was assessed with a translated version of the System Usability Scale. We reported the distribution of clinical characteristics in our participants.

Results:

Step counts per day increased over 4 weeks in a dose-dependent pattern (mean ± standard deviation: minimal = 1064 ± 1030, moderate = 1689 ± 2060, large = 2745 ± 3817). The usability of the STEPWISE app (System Usability Scale) was perceived as excellent (mean ± standard deviation: 86.6 ± 12.7).

Discussion and Conclusions:

Our findings support the notion that a titrated increase in daily step count is feasible over 4 weeks. This motivates and supports further development of a smartphone application to increase physical activity in people with manifest PD. If effective, this behavioral intervention could provide an accessible option for people with PD worldwide.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content available at: http://links.lww.com/JNPT/A516).
Lessons Learned from a Quality Improvement Initiative to Increase COVID-19 Vaccination in Hospitalized Children
Authors: Young Daniel G. , Rogers Cortney S. , Mayefsky Isaac , Neufeld Thomas , Niesen Angela , Reich Patrick J. , Kao Carol M. , Srinivasan Mythili
Published: January 2025

Introduction:

Pediatric coronavirus disease 2019 (COVID-19) vaccination rates in the United States remain lower compared with adults. We aimed to (1) implement a quality improvement initiative to increase COVID-19 vaccination 2-fold in hospitalized patients 12–21 years of age from 4.7% during the baseline period (August 10, 2021–November 1, 2021) to 9.4% during the intervention phase (November 2, 2021—March 31, 2023) and (2) assess the importance of existing interventions and obtain feedback for future interventions to increase COVID-19 vaccination via a provider survey.

Methods:

We conducted the quality improvement initiative in the inpatient units of a freestanding children’s hospital. Interventions included provider education, electronic medical record best practice alerts, monthly competition, parental counseling to increase vaccine acceptance, and ensuring vaccine availability. The primary outcome measure was the percentage of hospitalized patients 12–21 years of age who received COVID-19 vaccine. Providers addressing COVID-19 vaccination with patients, as documented by COVID-19-specific problem lists, were a process measure. Length of stay was a balancing measure.

Results:

Although COVID-19 vaccination increased 1.6-fold during the initial 5 months of interventions, the interrupted time series analysis did not show a significant impact of our interventions on vaccination. Documentation of COVID-19 vaccine-specific problem lists increased 1.9-fold during most of the intervention period. There was no significant (P = 0.61) difference in length of stay between children in the baseline and intervention groups.

Conclusions:

Despite our best efforts, we could not increase the number of COVID-19 vaccinations in our patients. Lessons learned suggest that creating a nurse-driven COVID-19 vaccine screening/ordering protocol and integrating COVID-19/influenza vaccination annually during influenza season can potentially increase vaccination rates, but further research is required.
Keep Moving: Sustainability of an Early Mobility Protocol in an Academic Pediatric ICU
Authors: Domann Jenna E. , Davies Lindsay E. , Zivick Elizabeth E. , Johnson Laken , Keller Everette P. , Walz Alice A.
Published: January 2025

Introduction:

Mobilization protocols are safe and feasible for critically ill pediatric patients in the intensive care unit (ICU), but barriers exist to sustainability. This study described a focused early mobility protocol, sustained over 5 years, which is on time for therapy consults and patient mobilization at a single institution.

Methods:

A formal ICU mobility protocol was implemented as part of a unit-wide ICU liberation bundle. As part of the ongoing program assessment, over a specific 3-month timeframe annually from 2017 to 2023, the number of physical and occupational therapy (PT/OT) consults, mobilization rate, and time to PT/OT consult were analyzed. In addition, in 2023, we assessed specific barriers to early PT/OT consultation.

Results:

Annually, for each study timeframe, there was a sustained decrease in time to therapy consult from a mean of 3.8 days for PT and 7 days for OT in 2017 to 1.9 and 1.6 days, respectively, in 2023. Similarly, the mobilization rate increased from 20.3 sessions per 100 patient days in 2017 to 48.2 in 2023. There was a trend toward missed or delayed therapy consults at times of higher ICU census. No adverse events were associated with mobilization.

Conclusions:

An ICU early mobility protocol leads to a sustained decrease in the time to therapy consultation, an increase in the number of therapy consults, and an increase in the mobilization rate. Future interventions should focus on mitigating barriers to timely consultation, specifically at times of higher ICU census.
Assessing Gaps in Integrated HIV and STI Testing Among New York State-Funded Providers by Pre-Exposure Prophylaxis Status: Implications for Status-Neutral Programming
Authors: Tesoriero James M. , Boos Elizabeth M. , Adamashvili Natalia , Massaroni Ronald , Maglaperidze Tatia , O’Grady Thomas J.
Published: January 2025

Background:

In the United States, up to 75% of primary care patients go untested for HIV each year, and nearly two-thirds of adults report never having been tested for HIV. Integrated HIV and STI testing, combining these tests into a single visit, is recommended as a status neutral approach to prevention.

Setting:

Over 200 New York State Department of Health-funded primary care clinics, hospitals, health centers and community-based organizations funded to conduct integrated screening.

Methods:

We analyzed weekly testing data from December 2022 to January 2024 to prospectively evaluate whether integrated HIV and STI testing events and results occurred within 30 days of each other. We also assessed group differences in integrated testing by sex at birth, gender, race/ethnicity, risk, organization type, and pre-exposure prophylaxis (PrEP) status using Pearson’s Chi-square tests and calculated prevalence ratios using log binomial models stratified be PrEP usage. Analyses were restricted to individuals with an HIV-negative status.

Results:

Integrated testing was completed for 69% for individuals on PrEP and 39% for those not taking PrEP, with significant differences observed across all client-specific categories at p < 0.001. Except for age group, variations in integrated screening levels by client characteristics were similar by PrEP status. Individuals who identified as female at birth, as non-Hispanic Black, without an elevated risk, and those tested in non-hospital settings were significantly less likely to experience integrated screening. HIV-test reactivity was 0.04% among integrated testers and 0.15% for HIV-only testers. STI-test reactivity was 4.9% among integrated testers and 7.8% for STI-only testers.

Conclusions:

A significant gap was identified in integrated testing among providers specifically funded to perform it, resulting in missed opportunities for identification of HIV and other sexually transmitted infections. Integrating HIV and STI testing at a systems level will require significant changes to the perceived individual- and provider-level risks and benefits associated with testing.
Optimizing inpatient diabetes management with the diabetes dashboard
Authors: Wang Wenyong , Puri Gaurav , Sly Benjamin , Samadbeik Mahnaz , Ng Soong , Newton Jenna , Sullivan Clair
Published: January 2025

Inpatient diabetes management presents a complex challenge that is distinct from outpatient management. This is due to acute changes in physiology, medication regimens, and eating patterns associated with hospitalization, alongside the condition's prevalent and variable nature. The conventional systems for managing glycemic control in hospital have been found lacking, with gaps in data integration, decision support, and timely intervention. Queensland Health's development and adoption of the Glucose Management View and the Glucose Assessment for Inpatients (GAIN) dashboard represents a significant leap forward. The TIDieR checklist and guide have been used to report the implementation of these two interventions. The Glucose Management View, available within an individual's electronic medical record, provides an overview of demographics, relevant medication details, pathology data, and blood glucose levels. This cohesive and intuitive interface enhances individual patient trend visibility and facilitates diabetes medication prescribing. GAIN consolidates all diabetes-related patient data within the hospital into a single interface, enabling clinicians to monitor glycemic status across the whole cohort in near real-time, promoting a proactive approach to diabetes management. The future of inpatient diabetes care looks toward the incorporation of machine learning and artificial intelligence (AI) to predict adverse events and streamline care further. However, significant gaps remain in the deployment of these technologies, indicating a need for more comprehensive development and testing of all phases of the AI lifecycle, before integration into clinical practice.

Spanish abstract:

http://links.lww.com/IJEBH/A308
Safety and efficacy of lamivudine/dolutegravir vs. bictegravir/emtricitabine/tenofovir alafenamide in antiretroviral-naive adults with HIV-1 infection in Shanghai, China: a single-centre retrospective study
Authors: Yang Junyang , Wang Lin , Zhang Xiaoran , Liu Li , Shen Yinzhong , Qi Tangkai , Wang Zhenyan , Song Wei , Tang Yang , Xu Shuibao , Sun Jianjun , Chen Youming , Shen Yihong , Chen Jun , Zhang Renfang
Published: January 2025

Introduction. Lamivudine plus dolutegravir (3TC/DTG) and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimens are commonly used as first-line treatments for people living with human immunodeficiency virus (HIV) (PLWH) worldwide.

Gap Statement. There are limited comparative data on the antiviral activity and safety between these regimens in ART-naive PLWH, particularly in China, where the 3TC/DTG regimen was integrated into first-line therapy in 2021 and gained broader adoption after its inclusion in the National Health Insurance in 2022.

Aims. This study aims to provide real-world evidence comparing the 3TC/DTG regimen to the B/F/TAF regimen in ART-naive PLWH in China.

Methodology. This retrospective study enrolled PLWH initiating ART with either 3TC/DTG or B/F/TAF in Shanghai from January 2020 to January 2023. Demographic characteristics and clinical information were collected and compared for each patient.

Results. A total of 380 eligible, ART-naive PLWH were included, with 190 patients in the 3TC/DTG group and 190 patients in the B/F/TAF group. Following the initiation of ART, most patients (94.1 and 89.3% for 3TC/DTG and B/F/TAF groups, respectively) achieved viral suppression (<50 copies of HIV RNA per millilitre) at week 24. The CD4 cell count significantly increased from a baseline of 301.3±185.8 cells per microlitre to 479.5±229.3 cells per microlitre at week 36 for the 3TC/DTG group and from 289.2±188.8 cells per microlitre at baseline to 487.8±234.2 cells per microlitre at week 36 for the B/F/TAF group. Both groups experienced an increase in blood lipid levels after initiating ART, with higher levels of high-density lipoprotein cholesterol (HDL-C) observed in the 3TC/DTG group compared with the B/F/TAF group. Renal and hepatic function indicators remained stable in both groups.

Conclusions. 3TC/DTG demonstrates similar antiviral efficacy to B/F/TAF and does not significantly impact liver and kidney functions. Patients receiving 3TC/DTG showed higher plasma HDL-C levels compared with those on B/F/TAF, which confer long-term clinical benefits in reducing cardiovascular risk.
Frontal eye field neurons predict “anti-Bayesian” but not Bayesian judgments of visual stability across saccades
Authors: Subramanian Divya , Pearson John , Sommer Marc A.
Published: January 2025

Bayesian models, in which priors are used to optimally compensate for sensory uncertainty, have had wide-ranging success in explaining behavior across sensorimotor contexts. We recently reported, however, that humans and monkeys use a combination of Bayesian and non-Bayesian strategies when making categorical judgments of visual stability across saccades. While they used priors to compensate for internal,movement-driven sensory uncertainty, consistent with Bayesian predictions, they decreased their use of priors when faced with external,visual imageuncertainty—an “anti-Bayesian” adjustment consistent with the use of a simple classifier. Here, we tested for neural correlates of these Bayesian and classifier-based strategies in the frontal eye field (FEF), a prefrontal region shown to be important for the perception of visual stability across saccades. We recorded from single FEF neurons while two rhesus macaques performed the internal (motor) and external (image) noise tasks in each session, interleaved trial by trial. FEF activity correlated with and predicted the anti-Bayesian, but not the Bayesian, behavior. These results suggest that the two computational strategies for visual stability are implemented by distinct neural circuits and provide a first step toward an integrated understanding of the computational and neural mechanisms underlying visual perception across saccades.
S9BactDB: A database for S9 family of proteases in bacterial genomes
Authors: Nayak Soumya , Sowdhamini Ramanathan
Published: January 2025

S9 family proteins are serine proteases, divided into four subfamilies, involved in several functions associated with cell signalling, defence response and development. However, the annotation, characterization and statistical information are lacking. This is compounded by the huge number of bacterial genomes available. Hence, we have performed computational searches for S9 family peptidases as a step towards organising, curating the sequences and classifying into subfamilies. We have analysed annotated S9 family sequences from ∼32000 bacterial genomes/proteomes. All the curated information are presented as S9BacDB database (http://caps.ncbs.res.in/S9BactDB), provided in a user friendly way. The database provides various features such as information on the assemblies used (assembly, BioProject and BioSample details of each strain), the annotated POPs and their statistical distribution, unique domain architectures and the associated sequences and curated phylogenetic analysis. In addition, it provides the unique motifs and the associated information for Prolyl OligoPeptidases (POP) subtypes. An ML model is also integrated that can classify recognised sequences into a S9 sub family category. In conclusion, S9BactDb is a comprehensive platform that provides meticulously curated data on statistical/bioinformatics analysis of all S9 family proteins originating from fully sequenced bacterial genomes in the RefSeq database.
Conservation of southern yellow-cheeked gibbons (Nomascus gabriellae) in the Anthropocene
Authors: Piskovska Pavla , Piskovsky Vit , Cheyne Susan
Published: January 2025

The endangered southern yellow-cheeked gibbons (Nomascus gabriellae) occupy a fragmented habitat in Vietnam and Cambodia, with declining populations due to hunting, habitat loss and climate change. This study integrates population viability modelling with expert surveys to offer comprehensive insights into the species’ current state and its future prospects in a human-shaped world. Our modelling confirms the current population decline and suggests that a reduction in habitat loss and hunting is necessary to save this unique species from extinction. While declining habitat poses a long-term extinction risk, the current hunting rates threaten the species’ survival on the timescale of several decades. Crucially, large populations in Phnom Prich and Keo Seima Wildlife Sanctuaries and Cat Tien, Chu Yang Sin and Bu Gia Map National Parks play a key role in the survival of this species, as does the connectivity of these habitats. The expert surveys confirm the priority of protecting large populations and provide specific conservation actions for the case of Cat Tien National Park that are based on systematic stakeholder mapping. Altogether, this work assesses the population viability of southern yellow-cheeked gibbons in the Anthropocene and suggests conservation strategies that incorporate both ecological and social aspects.

Graphical Abstract

Highlights

Southern yellow-cheeked gibbons are at risk of extinction due to hunting, habitat loss and degra- dation.

Habitat loss poses a long-term risk while hunting endangers southern yellow-cheeked gibbons on the timescale of the following few decades.

Protecting large populations in Phnom Prich and Keo Seima Wildlife Sanctuaries and Cat Tien, Chu Yang Sin and Bu Gia Map National Parks plays a key role in saving southern yellow-cheeked gibbons from extinction.

Specific conservation actions based on a systematic stakeholder mapping are identified for Cat Tien National Park.
Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance
Authors: Klope Matthew T. , Talukder Poulami , Blank Brian R. , Chelebieva Sevil , Chen Jun , Fontaine Shaun D. , Gonciarz Ryan L. , Jaishankar Priyadarshini , Lee Grace J. , Legac Jennifer , Mathur Vineet , Narayan Avani , Okitwi Martin , Orena Stephen , Settineri Nicholas S. , Tapia Juan , Taremwa Yoweri , Tumwebaze Patrick K. , Vinod Aswathy , Burrows Jeremy N. , Rosenthal Philip J. , Cooper Roland A. , Renslo Adam R.
Published: January 2025

For over two decades, artemisinin-based combination therapy (ACT) has been the standard of care for the treatment of uncomplicated falciparum malaria. However, artemisinin partial resistance (ART-R) is now prevalent in Southeast Asia and has emerged in eastern Africa, threatening ACT efficacy. Mechanistically, ART-R results from an endocytosis defect that limits concentrations of host-derived free heme in the parasite digestive vacuole, allowing early ring-stage parasites to survive exposure to the artemisinin component of ACT. The artemisinin-inspired 1,2,4-trioxolane artefenomel exhibits an extended pharmacokinetic exposure profile that predicts efficacy against ART-R parasites. Unfortunately, the development of artefenomel was halted recently after almost a decade of clinical trials. Herein, we describe the discovery of RLA-4735 and its single-enantiomer form RLA-5764, next-generation antimalarial trioxolanes that exhibit excellent in vitro potency againstPlasmodium falciparumand single-exposure efficacy in a murineP. bergheimodel, thus retaining many of the favorable pharmacokinetic and pharmacodynamic properties of artefenomel while markedly improving solubility and development potential. InP. falciparumsamples collected from patients in Uganda in 2019 and 2023, ex vivo ring-stage survival assays revealed the emergence of the ART-R phenotype over this timeframe, and furthermore demonstrated markedly superior activity of artefenomel and RLA-4735 as compared to dihydroartemisinin (the active metabolite of artemisinin components of ACTs) against ART-R parasites. Overall, our findings suggest a role for next-generation trioxolanes in addressing ART-R, and present a potent new, artefenomel-adjacent chemotype with good potential to deliver new development candidates.

Summary Sentence

Klope et. al. described the discovery and in vivo characterization of antimalarial endoperoxides effective against artemisinin-resistant parasites as potential development candidates for uncomplicated, blood-stage malaria.
Novel Single-Cell Multiomics Approach to Analyze Replication Timing and Gene Expression in Mouse Preimplantation Embryos
Authors: Shetty Anala V. , Steer Clifford J. , Low Walter C.
Published: January 2025

Analysis of a cell’s replication timing (RT) provides insight into how genes replicate, early or late, during the S-phase of the cell cycle. RT is cell-type specific, inheritable, and has been correlated to gene expression in normal and diseased states. However, most studies have been limited to somatic cells. Very little is known about RT control in early mouse embryos, and how it correlates with the start of transcription during zygote gene activation (ZGA), at the 2-cell stage. In this study, we developed a novel in-house single-cell multiomics approach to simultaneously analyze RT and gene expression in individual cells of the mouse 1-cell, 2-cell, and 4-cell embryos. We detected that RT was established at the 1-cell stage prior to ZGA. Surprisingly, we observed that the coordinated RT and gene expression control was different in early totipotent embryos, compared to previously published studies in somatic cells. Late replicating regions correlated with higher gene expression and open chromatin in the early developing embryos. Lastly, we performed an integrated pseudo time trajectory analysis combining RT and gene expression information per cell.
Network Pharmacognosy ofGalphimia glauca: Mapping the Molecular Landscape of a Traditional Mexican Medicinal Plant
Authors: Acosta María José Cambero , de Anda Jáuregui Guillermo
Published: January 2025

This study explores the pharmacological landscape ofGalphimia glauca, a traditional Mexican medicinal plant known for its sedative and anti-inflammatory effects. Using network pharmacognosy, we analyzed the interactions ofG. glauca’s bioactive compounds, Galphimines A-I, with human protein targets. SwissTargetPrediction identified 214 unique protein targets across the galphimines, revealing a core-periphery structure in a bipartite network where 41 targets are shared among all compounds. Further interaction analysis using STRING-DB generated a dense protein-protein interaction network comprising 1,386 connections. Centrality analysis highlighted proteins such as SRC, MTOR, and MAPK3 as key nodes involved in cell growth, proliferation, and immune regulation pathways, suggesting these as pivotal mediators ofG. glauca’s pharmacological effects. Community detection with the Walktrap algorithm further segmented the network into functionally relevant modules linked to cell survival, immune response, and inflammation, reflecting the therapeutic effects historically attributed toG. glauca. Our findings underscore the plant’s multi-target therapeutic potential and highlight the value of network-based approaches in understanding traditional medicine. This work lays the groundwork for further studies aimed at refining therapeutic strategies based onG. glauca’s bioactive compounds and suggests network pharmacognosy as a promising tool for assessing other traditional medicinal plants.
Green-synthesized silver and iron nanoparticles fromAlstonia booneiandTerminalia catappa asantimalarial agents in mice models
Authors: Abuh Ojomona O. , Surakat Olabanji A. , Azeez Luqmon A. , Rufia Akinlabi M. , Fasasi Kamilu A. , Adeleke Monsuru A.
Published: January 2025

Malaria a major health scourge of high impact in sub-sahara, with a major control-drawback on issues of resistance of the parasite to antimalaria. Nanoparticles have been investigated for their capacity to effectively deliver antimalarial drugs to kill the parasites, avoid drug resistance evolution and maintain a low toxic side effects. This study investigated the antiplasmodial efficacies of two plant green-synthesized with AgNO3and FeSO4salts againstPlasmodium bergheiinfected mice using, an acute toxicity test (LD50) of theTerminalia-catappaAgNPs (TCA),Alstonia-booneiAgNPs (AA),Terminalia-catappaFeSO4(TCF) andAlstonia-booneiFeSO4(AF) in accordance with Lorke’s method. The LD50was above 5000 mg/kg of TCA and AA while 223.6 mg/kg in TCF and AF. Each nanoparticles exhibited high dose dependentP. bergheiinhibition which was 62.20 % and 75.6 % in the TCA 200 mg/kg AA 100 mg/kg, 61.5 % and 75.3 % in the TCF 300 mg/kg and AF 200 mg/kg and doses in the curative groups, 92. 4 % and 93.1 % for TCA 100 mg/kg, AA 100 mg/kg 94.1 in 100 mg/kg dose and AF had 92.1 % at 300 mg/kg doses in the prophylactic groups. The groups treated with orthodox drugs had low parasitemia while the negative control recorded high parasitemia. There was no significant difference (P ˃ 0.05) in the mean change of the dosage in the different nanoparticles. These findings revealed all nanoparticles possesses a dose-dependent curative and prophylactic antiplasmodial activity and calls for their development and standardization as effective and readily available antimalarial options.
Climate warming drives pulsed-resources and disease outbreak risk
Authors: Fay Rémi , Gamelon Marlène , Porphyre Thibaud
Published: January 2025

Climate influences the risk of disease transmission and spread through its direct effects on the survival and reproduction of hosts and pathogens. However, the indirect influences of climate variation, as those mediated by food resources on host demography, are often neglected. Pulsed-resources produced by oak trees in temperate forests constitute important resources for seed consumers and strongly depend on temperatures. Using an individual-based model, we provide a theoretical exploration of the influence of climate warming on the dynamic of the African swine fever (ASF) in the seed consumer wild boar (Sus scrofa), considering both direct and indirect temperature effects. We show that climate warming directly decreases the persistence of the virus in the environment, but also increases the production of acorns with cascading effects on the seed consumer host species. Integrating these climatic effects suggests a decrease of ASF spread under future warmer conditions. Importantly, food-mediated indirect effects of climate may outweigh direct effects, reversing in some situations the predictions of epidemic dynamics under climate change. This shows that anticipating future epidemic risks requires a deep understanding of ecological systems, including all direct and indirect climatic effects.
Discovery of Isobavachin, a natural flavonoid, as an Apolipo-protein E4 (ApoE4) structure corrector for Alzheimer’s disease
Authors: Patil Sachin P. , Kuehn Bella , McCullough Christina , Bates Dean , Hazim Hadil , Diallo Mamadou , Francois Naomie
Published: January 2025

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by extensive neurodegeneration and consequent severe memory loss. Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for AD, with its pathological effects linked to structural instability and altered interactions with lipids and other important disease proteins including amyloid beta (Aβ) and tau (τ). Therefore, correcting and stabilizing the ApoE4 structure has emerged as a promising therapeutic strategy for mitigating its detrimental effects. In this study, we investigated naturally occurring bioavailable flavonoids as ApoE4 stabilizers, focusing on their potential to modulate ApoE4 structure and function. Comprehensive investigation of a focused database using our integrated computational and experimental screening protocol led to the identification of Isobavachin as a potential corrector and stabilizer of ApoE4 structure. In addition, a few other bioavailable flavonoids with similar stabilizing properties were identified, albeit to a much lesser extent as compared to Isobavachin. The findings support the therapeutic potential of flavonoids as ApoE4 modulators and highlight Isobavachin as a lead candidate for further preclinical evaluation. These results provide new insights into the pharmacological targeting of ApoE4 and open avenues for the development of flavonoid-based, ApoE-directed therapies for AD.
Phage Mu Utilizes the Sliding Clamp for Late Gene Transcription
Authors: Ho Khang , Harshey Rasika M.
Published: January 2025

MuC, along with core RNAP and σ70, is required for transcription of late genes of phage Mu. We observed that overexpression of MuC is lethal inE. coliand that host replication was over-initiating under these conditions. Suppressors of MuC lethality occurred in dnaA, diaA, and dnaX, genes involved in initiation of DNA replication. We hypothesized that lethality was likely due to increase in ATP-DnaA levels, which are normally kept in check by Hda-DnaN (β clamp). We noticed that MuC harbors a well-defined motif for interaction with the β clamp. We provide experimental support for this interaction and show that disrupting it through mutations in the clamp-binding motif on MuC, expressed from both plasmid and the phage genome, abrogated transcription from a MuC-dependent promoter as well as production of viable phage, respectively. Furthermore, we show that inactivation of β-clamp specifically inactivates C-dependent transcription but not σ70-dependent transcription. We conclude that MuC requires the b sliding clamp for transcribing late phage genes. To the best of our knowledge, this is the first demonstration of the involvement of the clamp, a processivity factor essential for DNA replication, for transcription byE. coliRNAP.
Tissue-specific modulation of NADH consumption as an anti-aging intervention in Drosophila
Authors: Yadav Shweta , Pan Xingxiu , Li Shengxi , Martin Paige LaRae , Hoang Ngoc , Chen Kejin , Karhadkar Aditi , Malhotra Jatin , Zuckerman Austin L , Munan Subrata , Klose Markus K , Wang Lin , Cracan Valentin , Parkhitko Andrey
Published: January 2025

Aging is characterized by extensive metabolic dysregulation. Redox coenzyme nicotinamide adenine dinucleotide (NAD) can exist in oxidized (NAD+) or reduced (NADH) states, which together form a key NADH/NAD+ redox pair. Total levels of NAD decline with age in a tissue-specific manner, thereby playing a significant role in the aging process. Supplementation with NAD precursors boosts total cellular NAD levels and provides some therapeutic benefits in human clinical trials. However, supplementation studies cannot determine tissue-specific effects of an altered NADH/NAD+ ratio. Here, we created transgenic Drosophila expressing a genetically encoded xenotopic tool LbNOX to directly manipulate the cellular NADH/NAD+ ratio. We found that LbNOX expression in Drosophila impacts both NAD(H) and NADP(H) metabolites in a sex-specific manner. LbNOX rescues neuronal cell death induced by the expression of mutated alpha-B crystallin in the Drosophila eye, a widely used system to study reductive stress. Utilizing LbNOX, we demonstrate that targeting redox NAD metabolism in different tissues may have drastically different outcomes, as the expression of LbNOX solely in the muscle is much more effective for rescuing paraquat-induced oxidative stress compared to whole-body expression. Excitingly, we demonstrate that perturbing NAD(P) metabolism in non-neuronal tissues is sufficient to rejuvenate sleep profiles in aged flies to a youthful state. In summary, we used xenotopic tool LbNOX to identify tissues and metabolic processes which benefited the most from the modulation of the NAD metabolism thereby highlighting important aspects of rebalancing the NAD and NADP pools, all of which can be translated into novel designs of NAD-related human clinical trials.
Studying
π+π−
photoproduction beyond Pomeron exchange
Authors: Bibrzycki Łukasz , Hammoud Nadine , Mathieu Vincent , Perry Robert J. , Akridge Alex , Fernández-Ramírez César , Montaña Gloria , Pilloni Alessandro , Rodas Arkaitz , Shastry Vanamali , Smith Wyatt A. , Winney Daniel , Szczepaniak Adam P. ,   Joint Physics Analysis Center
Published: January 2025

Forward photoproduction of π+π− pairs with invariant mass of the order of mρ∼770  MeV is traditionally attributed to Pomeron exchange. Based on a detailed analysis of the CEBAF Large Acceptance Spectrometer photoproduction data collected at photon energies below 4 GeV, it is shown from a study of the angular moments that the dynamics of two-pion photoproduction for |t|≳0.5  GeV2 cannot be explained by Pomeron exchange alone. This motivates the development of a new theoretical model of two-pion photoproduction which incorporates both two-pion and pion-nucleon resonant contributions. After fitting free parameters, the model provides an excellent description of the low moments of the angular distribution measured at CLAS and enables an assessment of the relative contributions of particular production mechanisms and an interpretation of the various features of the data in terms of these mechanisms.

Published by the American Physical Society
2025