bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of hip fracture patients on direct oral anticoagulants: a survey of orthopaedic trauma surgeons, systematic review, and meta-analysis
Authors: Spitler Clay , Rutz Robert , Blackwood Nigel , Wally Meghan , Johnson Joseph , Krause Peter , Ahn Jaimo , Mohammed Zuhair , McClure Mark , Billings Rebecca , Yu Ziqing , Yeager Matthew ,   Orthopaedic Trauma Association's Evidence-Based Quality Value and Safety Committee
Published: January 2025

Objectives:

This systematic review examined the literature regarding management of fracture patients who take direct oral anticoagulant (DOAC) medications, with a focus on delay in surgical treatment, and need for transfusions. In addition, a survey of orthopaedic trauma surgeons was conducted to gain insight on current practices.

Data Sources:

A review of PubMed, Cochrane, Embase, and Scopus databases was performed from inception through March 2024, including English language publications.

Study Selection:

Studies were included if they reported time to surgery and transfusion rates among fracture patents who were taking DOAC medications. Additional data points were collected on an “if-reported” basis, including mortality, venous thromboembolism, and bleeding complications.

Data Extraction:

In all, 4546 abstracts were screened. Full-text review was conducted on 86 publications, and 25 articles were included in the final analysis. Each article was independently screened by 2 reviewers, with disputes settled by a third reviewer. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) tool.

Data Synthesis:

Descriptive statistics are reported for overall study findings. Meta-analysis was performed for the variables “time to surgery” and “transfusion rate.”

Conclusions:

Our findings indicate that fracture patients taking DOACs experience longer delays before surgery but have equivalent transfusion rates compared with nonanticoagulated patients. Survey results indicate that surgeons do not delay operating on emergent or percutaneous cases, regardless of anticoagulant medications. In circumstances when they do delay, they are more likely to do so for patients taking DOAC medications.

Level of Evidence:

Level III, systematic review and meta-analysis of Level II and III articles.
Safety and efficacy of switching to 4-weekly albuvirtide plus daily dolutegravir in virologically suppressed HIV-1 adults: a 24-week study
Authors: xie Xiaoxin , Fu Yanhua , Gan Lin , yang Xiaoyan , Song Yebing , Song Chunli , Sun Fangfang , Guo Lei , Long Hai
Published: January 2025

Objectives:

Albuvirtide (ABT) is a long-acting fusion inhibitor. This study assessed switching to ABT 640 mg every 4 weeks plus daily Dolutegravir (DTG) in virologically suppressed adults with HIV-1.

Design and methods:

In this open-label, single-arm study, 10 participants with HIV-1 RNA <50 copies/mL switched to ABT plus DTG for 24 weeks. Safety, pharmacokinetics, viral load, and CD4+ T cell counts were assessed.

Results:

No serious adverse events occurred. Albuvirtide's steady-state trough concentration was 31.1 times higher than PA-IC90. All participants maintained virological suppression. CD4+ T-cell counts increased significantly after 24 weeks (P = 0.0462).

Conclusion:

Switching to 4-weekly ABT plus daily DTG demonstrated good safety, favorable pharmacokinetics, maintained virological suppression, and improved immune recovery. These findings support ABT's potential as a long-acting agent for simplifying HIV treatment.
Men’s voices on Long-acting Pre-Exposure Prophylaxis (LA PrEP) delivery modalities: Acceptability and Preferences among Cis-gender men and men who have sex with men in South Africa
Authors: Atujuna Millicent , Nyamaizi Alinda M. , Duby Zoe , Minnis Alexandra , Diaz Miranda , Palanee-Phillips Thesla , Tenza Siyanda , Reddy Krishnaveni , Nkomana Nqaba , Bekker Linda-Gail , Montgomery Elizabeth
Published: January 2025

Introduction:

In sub-Saharan Africa (SSA), cisgender men—in particular men who have sex with women (MSW) and, to a lesser degree, men who have sex with men (MSM)—are often under-represented in HIV prevention research, despite their own HIV risk and role in transmission cycles. As HIV prevention research on long-acting pre-exposure prophylaxis (LA PrEP) options expands in SSA, it is essential to engage these populations to ensure their acceptability. We investigated perceptions of implants and intramuscular injectables as LA PrEP delivery among MSW and MSM.

Methods:

In-depth interviews were conducted between October 2020 and March 2021with 40 MSW (n=20) and MSM (n=20), aged 18-35 years, self-reported as HIV-negative, sexually-active, and residing in resource-restricted communities in Cape Town and Johannesburg, South Africa. We explored factors influencing LA PrEP attitudes. Data analysis followed a thematic framework approach.

Results:

MSW and MSM found LA PrEP administration modes more acceptable than daily oral PrEP because they offered longer-lasting protection while reducing frequent clinic visits for refills. MSW voiced hesitancy around the use of ‘foreign products’, fearing infertility and congenital-disabilities in their future children. Both subgroups acknowledged the convenience of implants with long-dosing duration, but injections were deemed to be more discreet and familiar. Both groups described Implant use as potentially stigmatizing, with a greater chance of causing tissue scarring from insertion and removal procedures.

Conclusions:

Evidence relating to men’s engagement in HIV prevention and acceptable modalities of HIV prevention is limited. We found that both groups were enthusiastic about LA PrEP, informing the development of our subsequent clinical study to provide further insight into using placebo versions of LA PrEP and future implementation of LA PrEP options.

One-Sentence Summary:

LA PrEP acceptability and preference among men
The Use of Acellular Dermal Matrix May Not Increase 30-Day Complications in Direct-to-Implant Breast Reconstruction
Authors: Knoedler Samuel , Klimitz Felix J. , Friedrich Sarah , Schemet Lena , Broer P. Niclas , Cherubino Mario , Könneker Sören , Kim Bong-Sung , Pomahac Bohdan , Kauke-Navarro Martin
Published: January 2025

Background

Direct-to-implant (DTI) breast reconstruction offers immediate aesthetic and psychological benefits, but the role of acellular dermal matrix (ADM) remains debated. Using a multi-institutional database, this study evaluates and compares outcomes between ADM-assisted and non-ADM DTI procedures.

Methods

The American College of Surgeons National Surgical Quality Improvement Program database from 2008 to 2022 was queried to identify female patients who underwent DTI breast reconstruction for oncological purposes. Patients were divided into 2 groups: DTI breast reconstruction with ADM and without. Thirty-day postoperative complications were compared using multivariate analysis and propensity score matching.

Results

Among 10,177 patients, 45% (n = 4605) underwent ADM-assisted DTI, while 55% (n = 5572) had non-ADM DTI. While both groups showed comparable mean ages (ADM: 52 ± 12 years vs non-ADM: 51 ± 11 years; P = 0.190), ADM patients were significantly less likely to present with comorbidities such as obesity (ADM: 21.5% vs non-ADM: 26%; P < 0.001), hypertension (20.5% vs 2.6%; P = 0.01), diabetes (4.8% vs 5.1%; P = 0.002), and smoking history (6.4% vs 10.1%; P < 0.001). Still, surgical complication rates were comparable (ADM: 4.7%, non-ADM: 5.5%; P = 0.08), including superficial infections (2.0% vs 2.4%; P = 0.19), deep infections (0.6% vs 0.9%; P = 0.17), wound dehiscence (0.8% vs 1.0%; P = 0.24), and bleeding (0.6% vs 0.7%; P = 0.54). Medical complications were generally rare and also showed no significant differences (ADM: 1.4%, non-ADM: 1.7%; P = 0.27). Confounder-adjusted multivariable analysis and propensity score matching confirmed no increased risk of surgical (odds ratio 0.93, 95% confidence interval 0.75–1.16, P = 0.52) or medical complications (odds ratio 0.87, 95% confidence interval 0.59–1.26, P = 0.46).

Conclusions

The use of ADM in DTI breast reconstruction is not associated with a higher risk of short-term complications, supporting its continued use in clinical practice. This information is crucial for surgeons and patients in making informed decisions regarding the incorporation of ADM in DTI breast reconstruction.
Received and Desired Support Needs of Postoperative Bariatric Surgery Patients
Authors: Sink Katherine K. , Gibbon Sharmeta
Published: January 2025

Obesity is a worldwide health concern with one highly effective solution being bariatric surgery. The purpose of this descriptive study was to explore the experiences of postoperative bariatric surgery patients related to perceptions of helpful interventions for achieving and maintaining weight loss. Fifteen participants shared their perceived support received and their perceptions of desired support needed after bariatric surgery. The results indicated that the participants felt they primarily received support from their spouse/significant other and others who had surgery. They felt additional support was needed in the areas of nutrition, exercise, mental/emotional health, and expected stages of recovery, provided during the time when the information was needed. According to the participants, this support could be delivered in online educational modules or via telemedicine. While bariatric surgery can result in significant weight loss, ongoing support is necessary to help patients address postsurgical complications, adjustment to lifestyle modifications, maintenance of weight loss, and emotional support during times of stress.
Validation of a Pretransplant Risk Prediction Model for Early Allograft Dysfunction After Living-donor Liver Transplantation
Authors: Li Zhihao , Raptis Dimitri , Rammohan Ashwin , Gunasekaran Vasanthakumar , Hong Suyoung , Chen Itsuko Chih-Yi , Kim Jongman , Hervera Marquez Kris Ann , Hsu Shih-Chao , Kirimker Elvan Onur , Akamatsu Nobuhisa , Shaked Oren , Finotti Michele , Yeow Marcus , Genedy Lara , Braun Julia , Yebyo Henock , Dutkowski Philipp , Nadalin Silvio , Boehnert Markus U. , Polak Wojciech G. , Bonney Glenn K. , Mathur Abhishek , Samstein Benjamin , Emond Jean C. , Testa Giuliano , Olthoff Kim M. , Rosen Charles B. , Heimbach Julie K. , Taner Timucin , Wong Tiffany CL. , Lo Chung-Mau , Hasegawa Kiyoshi , Balci Deniz , Cattral Mark , Sapisochin Gonzalo , Selzner Nazia , Jeng Long-Bin , Joh Jae-Won , Chen Chao-Long , Suh Kyung-Suk , Rela Mohamed , Broering Dieter , Clavien Pierre-Alain
Published: January 2025

Background.

Early allograft dysfunction (EAD) affects outcomes in liver transplantation (LT). Existing risk models developed for deceased-donor LT depend on posttransplant factors and fall short in living-donor LT (LDLT), where pretransplant evaluations are crucial for preventing EAD and justifying the donor’s risks.

Methods.

This retrospective study analyzed data from 2944 adult patients who underwent LDLT at 17 centers between 2016 and 2020. We developed a logistic regression model to predict EAD based on this development cohort. We used data from 1020 patients at the King Faisal Transplant Center for external validation.

Results.

In the development cohort, 321 patients (10.9%) experienced EAD. These patients had poorer health status, more liver decompensation, and higher requirements of hospitalization than those without EAD. Multivariable logistic regression identified independent pretransplant predictors of EAD: laboratory Model for End-Stage Liver Disease score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.09), the necessity for hospitalization at the time of transplant (OR, 2.58; 95% CI, 2.00-3.30), and graft weight in kilogram (OR, 0.27; 95% CI, 0.17-0.45). Using these predictors, we developed the model for EAD after LDLT, which demonstrated strong discriminative ability in the development cohort with an area under the curve (AUC) of 0.71 (95% CI, 0.68-0.74). The model maintained high discrimination during internal validation (AUC, 0.70; 95% CI, 0.67-0.73) and showed a modest reduction in discriminative power in external validation (AUC, 0.65; 95% CI, 0.61-0.68).

Conclusions.

EAD post-LDLT is influenced by the recipient’s pretransplant health condition and the graft weight. Integrating the model for EAD after LDLT into the pretransplant process of pairing donors and recipients can enhance the safety and efficacy of LDLT.
Lower Limb Compartment Syndrome Among Colorectal Patients: Risk Factors and Proposed Guidelines
Authors: Suresh Reena S , Stem Miloslawa , Winland Ama J , Tassinari Stefano , Obias Vincent J , Gabre-Kidan Alodia , Gearhart Susan L , Najjar Peter A
Published: January 2025

Background:

Lower limb compartment syndrome (LLCS) is a rare but potentially devastating complication of prolonged lithotomy positioning in colorectal surgery. The mechanisms appear to be related to prolonged pressure on muscle compartments, leading to hypoperfusion followed by reperfusion injury. This study aims to identify the incidence of LLCS after colorectal surgery and identify associated risk factors to inform evidence-based prevention strategies.

Study Design:

Adults from the American College of Surgeons-National Surgical Quality and Improvement Program (2006-2022) undergoing colorectal surgery were included. The primary outcome was postoperative compartment syndrome leading to fasciotomy. Patients with concurrent vascular procedures and embolism diagnoses were excluded. The association between operative time and fasciotomy was assessed using multivariable logistic regression.

Results:

Among 773,981 patients, 35 underwent fasciotomy within 2 days of their colorectal procedure. The median operative time was 388 minutes (IQR 165, 539) for the fasciotomy group and 162 minutes (IQR 113,320) for the non-fasciotomy group (p<0.001). Adjusted multivariable analysis demonstrated a time-response relationship between operative time and fasciotomy as the odds of fasciotomy was 3.5-fold higher after 3-5 hours and increased with longer operative time. In addition, other factors associated with fasciotomy included age <50 years, ASA IV-V, and preoperative transfusion.

Conclusions:

Providers should exercise caution when operating on younger patients in lithotomy position with an operative time over 3-5 hours, as prolonged operative time is associated with an increased risk of fasciotomy. Improving awareness alongside the development of guidelines for routine intraoperative lower extremity assessment can facilitate early recognition and prevention of LLCS.
Use of Small Bowel Follow Through in Management of Small Bowel Obstruction
Authors: Soult Alexa , Van Horn Alexandra , Sturm Emily , Sternick Molly , Burgess Jessica , Britt Rebecca
Published: January 2025

Background:

Small bowel obstructions (SBO) are a burden to healthcare. Despite a common disease, significant inconsistencies exist within management, specifically use of small bowel follow through (SBFT). We evaluated patients who had SBFT and the early versus late use of SBFT on outcomes.

Study Design:

A retrospective chart review was performed for 799 SBO patients admitted between 2012 and 2019. Patients between 18 and 89 were included and those that required emergent operations on admission were excluded. The groups were evaluated by having SBFT compared to not, and further delineated on SBFT performance before (early) or after (late) 48 hours.

Results:

Of the 799 patients with a SBO, 757(94.7%) patients had SBFT and 42(5.2%) patients did not. Of those 757, 476(62.8%) performed early and 281(37.1%) completed late. In patients that received SBFT, the length of stay (LOS) was shorter (p<0.003). If patients were admitted to the surgical service, they were more likely to receive a SBFT (p<0.0042). When SBFT early, patients were more frequently admitted to an academic institution (p<0.0001) and to a surgical service (p<0.0001), had decreased LOS (p<0.001), decreased readmissions (p<0.0001), less likely to require surgery (p<0.0009), decreased time to operation (p<0.0001), and quicker operation to discharge (p<0.0005).

Conclusions:

The use of SBFT for SBO resulted in improved outcomes, especially if performed early. This is supportive of surgical service admission with more frequent early SBFT with decreased LOS. There is a propensity for those patients with prior operations to have SBFT later in hospital stay and may correlate with increased need for surgery, and the use of early SBFT may help resolve SBO. Implementing early SBFT may improve outcomes and an area of future endeavors.
Insights into the genome of Azotobacter sp. strain CWF10, isolated from an agricultural field in Central India
Authors: Roy Arindam , Ghosh Anwesha , Yash  , Mehra Prateeksha , Roy Sumit , Bhadury Punyasloke
Published: January 2025

Azotobacter sp. strain CWF10, an aerobic gram-negative, oval-shaped and motile bacterium, was isolated from the lateritic agricultural soil of Madhya Pradesh, India. The draft genome of the isolate is 5.7 Mb in size, consisting of 14 contigs with 65.09% G+C content. Average nucleotide identity (94.66%) and digital DNA–DNA hybridization (62%) calculation with the closest reference strains underpin the bacterium as a potential novel species. The bacterium has a plethora of plant growth-promoting genes that point towards the potential ability to enhance available nitrogen and biosynthesis of folic acid, among others. Siderophores such as vibrioferrin and crochelin A are also present in the genome and are known to regulate iron uptake. Overall, mining the genome of Azotobacter sp. strain CWF10 has revealed the potential of this strain for application in regenerative agriculture and sustaining soil health.
Flavobacterium magnesitis sp. nov. and Flavobacterium zubiriense sp. nov., two novel Flavobacterium species isolated from alkaline magnesite residues
Authors: Matos Leonor , Maccarrio Lorrie , Chung Ana Paula , Proença Diogo N. , Sørensen Søren , Morais Paula V. , Francisco Romeu
Published: January 2025

Three bacterial strains, designated FZUC8N2.13T, FBOR7N2.3T and FZUR7N2.5, were isolated from distinct magnesite residues in Spain. Phylogenetic and phylogenomic analysis places them within the genus Flavobacterium. Strains FBOR7N2.3T and FZUR7N2.5 share 100% of similarity in the 16S rRNA gene sequence, and both are most closely related to Flavobacterium cellulosilyticum AR-3-4T with which they share 97.5% of 16S rRNA gene similarity. Strain FZUC8N2.13T forms a distinct lineage most closely related to Flavobacterium lacustre IMCC36792T with 97.7% 16S rRNA gene similarity. The closest phylogenomic neighbours of these three strains are Flavobacterium flevense DSM 1076T, ‘Flavobacterium undicola’ BBQ-18T and Flavobacterium commune PK15T. The average nucleotide identity and digital DNA–DNA hybridization values between the three strains and closest members of the genus Flavobacterium are below the threshold values of 95% and 70%, respectively. Strains FZUC8N2.13T, FBOR7N2.3T and FZUR7N2.5 stain Gram-negative, are rod-shaped and form yellow colonies. Optimum growth occurs at 25 °C and pH 7. The genomic G+C contents are 33.4 mol% for strain FZUC8N2.13T and 33.2 mol% for strains FBOR7N2.3T and FZUR7N2.5. The major isoprenoid quinone is menaquinone 6. The major fatty acids are summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) (22.6–31.1%), iso-C15 : 0 (13.6–16.2 %) and anteiso-C15 : 0 (8.7–10.5%). The polar lipids consist of two aminolipids, two aminophospholipids and one glycolipid. The phylogenetic, phylogenomic, phenotypic and chemotaxonomic data indicate that FZUC8N2.13T, FBOR7N2.3T and FZUR7N2.5 are distinct from the described species of Flavobacterium and should be classified as novel species, for which we propose the names Flavobacterium zubiriense for strain FZUC8N2.13T (=UCCCB 179T=CECT 30977T) and Flavobacterium magnesitis for strains FBOR7N2.3T (=UCCCB 178T=CECT 30976T) and FZUR7N2.5 (=UCCCB 216=CECT 31036).
Allometric studies on human- and pig-sized Delphinidae to understand resting metabolic rates with respiratory measurements
Authors: Suzuki Ippei , Niizuma Yasuaki , Inamori Daiki , Watanabe Yurie , Sato Katsufumi , Aoki Kagari
Published: January 2025

Exponential relationships between basal metabolic rate (BMR) and body mass are known in both terrestrial and marine mammals, with elevated BMR in the latter. However, it remains unclear whether the exponential relationship in marine mammals is different from that in terrestrial mammals. Metabolic rates of animals while resting at the water surface (resting metabolic rates: RMRs) were measured by breath-by-breath respirometry in two species of Delphinidae from temperate regions to elucidate the relationship between RMR and body mass in pantropical spotted dolphins (Stenella attenuate) and Risso’s dolphins (Grampus griseus) with body masses ranging from 71 to 386 kg. The RMRs of rough-toothed dolphins (83–123 kg), common bottlenose dolphins (143–220 kg), and killer whales (3,364–5,318 kg) were obtained from the literature for allometric analyses. Measured RMRs were 344 ± 39 and 1398 ± 160 ml O2min-1, respectively, which were 1.2–2.1 times higher than those predicted for similar-sized terrestrial mammals. A linear mixed-effects model showed the allometric mass exponent of 0.65 (95% CI: 0.54–0.76), which was closer to the 2/3-power of body mass than that of the widely observed 3/4-power commonly reported across a broad range of taxa. The new scaling relationship observed in the Delphinidae indicates that larger dolphins require less energy in aquatic environments, which is consistent with the theory of heat loss associated with a narrower surface area relative to larger volumes. This study suggested a different scaling relationship between aquatic and terrestrial mammals.
Internal/External Bacterial Sources of Subgingival Plaque Reconstitution
Authors: Gibb Andrew , Bhagirath Anjali , Jain Lavanya , Gibson Monica , Williamson Deanna , Altabtbaei Khaled
Published: January 2025

Objectives

The objectives were to quantify the contributions of internal (self) and external (familial) sources to the recolonization of the bacterial content of the subgingival plaque following professional prophylaxis and assess the effect of close-contact activities on modifying this contribution.

Materials and Methods

Families, each consisting of at least one preschool-aged child and at least one sibling, were recruited for this interventional cohort pilot study. Microbial samples were collected from various oral sites, including saliva, buccal mucosa, tongue, supragingival plaque, and subgingival plaque in all family members. Following the child’s oral prophylaxis, subgingival plaque samples were collected one week later. DNA from these samples was extracted and sequenced using the 16S rRNA gene and estimation of the sources were quantified using Bayesian source tracking models. Additional analyses using generalized linear mixed models, Phylofactorization, and Spearman correlations. Statistical significance was set at p<0.05.

Results

Child’s own subgingival plaque was the primary source of recolonization, contributing 63.7% to the microbial community one-week post-prophylaxis. Siblings contributed approximately 8%, a contribution significantly higher than that from parents, who contributed around 3% each (p<0.05). The analysis revealed a statistically significant positive correlation between the number of siblings and their bacterial contribution to the child’s subgingival plaque. Several close contact activities between parents and children were statistically associated with higher contribution (p<0.05, Spearman correlation). Additionally, 110 bacteria were statistically significantly different in their internal contribution compared to external, after accounting for household association, sample type, and family members (p<0.05, Phylofactor)

Conclusion

The findings challenge the traditional focus on parent-child transmission of oral microbes, highlighting the importance of studying families as a whole.
Enterovirus D68 2A protease causes nuclear pore complex dysfunction and motor neuron toxicity
Authors: Zinn Katrina M. , McLaren Mathew W. , Imai Michael T. , Jayaram Malavika M. , Rothstein Jeffrey D. , Elrick Matthew J.
Published: January 2025

The picornavirus Enterovirus D68 (EV-D68) is an important pathogen associated with acute flaccid myelitis (AFM). The pathogenesis of AFM involves infection of spinal motor neurons and motor neuron death, however the mechanisms linking EV-D68 infection to selective neurotoxicity are not well understood. Dysfunction of the nuclear pore complex (NPC) has been implicated in motor neuron injury in neurodegenerative diseases such as amyotrophic lateral sclerosis, and the NPC is also modified by picornavirus proteases during the course of infection. We therefore sought to determine the impact of EV-D68 proteases on NPC structure and function and their role in motor neuron toxicity. We demonstrate widespread disruption of NPC composition by EV-D68 2A and 3C proteases via the direct cleavage of a relatively small number of nucleoporins, notably Nup98 and POM121 by 2Apro. Using reporter systems, we demonstrate that 2Aproinhibits nuclear import and export of protein cargoes and also disrupts the permeability barrier of the NPC, while having no apparent effect on RNA export. We further show that 2Aprois toxic to induced pluripotent stem cell derived motor neurons by demonstrating a rescue of toxicity with 2Aproinhibitor telaprevir at concentrations that are insufficient to inhibit viral replication. This study expands our understanding of EV-D68 neuropathogenesis and provides a rationale for targeting the NPC or 2Aprotherapeutically in AFM.
A systematic review and ALE meta-analysis of cognitive control, motivation and effort-based decision-making in schizophrenia and mood disorders: Implications for multidimensional apathy
Authors: Lafond-Brina Giulia , Dormegny-Jeanjean Ludovic C. , Bonnefond Anne
Published: January 2025

Background

Apathy is present in about 50% of patients suffering from schizophrenia (SZ) and mood disorders (MD). Even though these two disorders are different, in psychiatry, apathy refers typically to the same unidimensional clinical entity, sharing the same pathophysiological processes and symptoms regardless of the underlying diagnosis. Neurology proposes another perspective: three forms of apathy —emotional, executive, and initiative— are related to a disturbance in motivational processing, cognitive control, and effort-based decision-making, respectively. We explored whether this latter model can be applied in psychiatry by identifying differences between SZ and MD through a PRISMA meta-analysis of imaging studies on motivational, cognitive control, and effort-based decision-making networks.

Methods

We searched the Sleuth BrainMap database for studies on SZ, MD, and/or healthy controls using tasks that explore motivation, cognitive control, and effort-based decision-making. Twenty-eight functional MRI studies were identified and included for a coordinate-based activation likelihood estimation analysis.

Results

In SZ, hypoactivity in the motivational structures, a specific hyperactivity in the right cerebellar vermis that has previously been linked to emotional blunting and apathy, and a lack of activation during effort-based decision-making that could imply an impaired reward processing, suggest a dominant form of emotional apathy. In MD, hypoactivity in both cognitive control and motivational structures, which has previously been linked to the co-occurrence of executive difficulty and amotivation, suggests a dominant mix of emotional/executive apathy.

Conclusions

Despite a small number of studies, our results could help target new individualized treatment strategies in precision psychiatry based on a multidimensional approach to apathy.

Graphical abstract

The results of this meta-analysis highlight different activation profiles in SZ and in MD during motivational, cognitive control, and effort-based decision-making tasks, suggesting a dominant form of emotional apathy in SZ and a dominant coexistence of emotional and executive apathy in MD.
Clinico-genomic features predict distinct metastatic phenotypes in cutaneous melanoma
Authors: Aprati Tyler J. , Day Chi-Ping , Lee Daniel , Pan Alexander , Jee Justin , Tarantino Giuseppe , Manos Micheal P. , Faulkner Hannah , Holovatska Marta M. , Khaddour Karam , Feng Catherine H. , Burke Kelly P. , Glettig Marc , Weaver Ohler Zoe , El Meskini Rajaa , Hodi F. Stephen , Haq Rizwan , Shoushtari Alexander N. , Schultz Nikolaus , Ishizuka Jeffrey , Gusev Alexander , Griffith Maryclare , Kehl Kenneth L. , Liu David
Published: January 2025

Metastasis drives mortality and morbidity in cancer. While some patients develop broad metastatic disease across multiple organs, others exhibit organ-specific spread. To identify mechanisms underlying metastatic organotropism, we analyzed clinico-genomic data from over 7,000 patients with metastatic cutaneous melanoma in three independent cohorts (one primary discovery and two validation cohorts including a nationwide electronic health record-derived deidentified database), leveraging machine learning approaches to clinical data. We found that female sex and increased tumor mutational burden associate with decreased metastatic potential, while older age associates with more lung and adrenal metastases. Using unsupervised analyses, patients clustered into five metastatic patterns: a "highly metastatic" cluster characterized by involvement of many organs, a "low metastatic" cluster characterized by few metastatic sites (mostly lymph node metastases), and three additional clusters each characterized by metastasis to specific sites (brain, lung, liver). Mutations in B2M and PTEN associated with increased overall metastatic potential. PTEN mutations were also associated with brain metastases but were enriched only in the "highly metastatic" cluster and not the brain-specific cluster. Mutations in GNAQ or GNA11 (GNA) associated with increased liver metastasis. To validate this association, we tested and demonstrated liver tropism in two GNA-mutant genetically engineered cutaneous melanoma mouse models of metastasis. Overall, our study elucidates distinct phenotypes of metastasis in patients with melanoma and identifies novel clinical and genomic associations that illuminate the clinical drivers of metastatic organotropism.
XDH-1 inactivation causes xanthine stone formation inC. eleganswhich is inhibited by SULP-4-mediated anion exchange in the excretory cell
Authors: Snoozy Jennifer , Bhattacharya Sushila , Fettig Robin R. , Asma Ashley Van , Brede Chloe , Warnhoff Kurt
Published: January 2025

Xanthine dehydrogenase (XDH-1) is a molybdenum cofactor (Moco) requiring enzyme that catabolizes hypoxanthine into xanthine and xanthine into uric acid, the final steps in purine catabolism. Human patients with mutations inxdh-1develop xanthinuria which can lead to xanthine stones in the kidney, recurrent urinary tract infections, and renal failure. Currently there are no therapies for treating human XDH-1 deficiency. Thus, understanding mechanisms that maintain purine homeostasis is an important goal of human health. Here, we used the nematodeC. elegansto model human XDH-1 deficiency using 2 clinically relevant paradigms, Moco deficiency or loss-of-function mutations inxdh-1.Both Moco deficiency andxdh-1mutations caused the formation of autofluorescent xanthine stones inC. elegans. Surprisingly, only 2% ofxdh-1null mutantC. elegansdeveloped a xanthine stone, suggesting additional pathways may regulate this process. To uncover such pathways, we performed a forward genetic screen for mutations that enhance the penetrance of xanthine stone formation inxdh-1null mutantC. elegans. We isolated multiple loss-of-function mutations in the genesulp-4which encodes a transmembrane transport protein homologous to human SLC26 anion exchange proteins. We demonstrated that SULP-4 acts cell- nonautonomously in the excretory cell to limit xanthine stone accumulation. Interestingly,sulp-4mutant phenotypes were suppressed by mutations in genes that encode for cystathionase (cth-2)or cysteine dioxygenase (cdo-1), members of the sulfur amino acid metabolism pathway required for production of the osmolyte taurine. Furthermore,cdo-1mRNA accumulated insulp-4mutant animals, mirroringcdo-1activation observed during hyperosmotic stress inC. elegansand mammals. We propose that loss of SULP-4-mediated anion exchange causes osmotic stress andcdo-1activation, a maladaptive response that promotes xanthine stone accumulation. Supporting the model that the osmotic stress response impacts xanthine stone accumulation, a mutation inosm-8that constitutively activates the osmotic stress response, also promoted xanthine stone accumulation in anxdh-1mutant background. Thus, our work establishes aC. elegansmodel for human XDH-1 deficiency and identifiessulp-4and the osmotic stress response governed bycdo-1as critical players in controlling xanthine stone accumulation.
Genome-wide exploration of the transcriptional regulatory landscape in the early-diverging fungusR. microsporusreveals pervasive DNA methyl adenine regulatory network
Authors: Lax Carlos , Baumgart Leo A. , Tahiri Ghizlane , Nicolás-Muñoz Natalia , Zhang Yu , Blaby Ian K. , O’Malley Ronan C , Ng Vivian , Navarro Eusebio , Grigoriev Igor V , Nicolás Francisco E. , Garre Victoriano
Published: January 2025

Genetic regulation mechanisms rely on complex transcriptional networks that are often difficult to decipher. The study of transcription factor (TF) binding sites and their targets has traditionally faced scalability challenges, hindering comprehensive cistrome analyses. However, the development of the DNA affinity purification and sequencing (DAP-seq) technique has allowed unprecedented large-scale studies at genome-wide level of TF binding with high reproducibility. In this study, we apply this technique to the human opportunistic pathogenR. microsporus, a mucoralean fungus belonging to the understudied group of early-diverging fungi (EDF). We characterize genome-wide binding sites of 58 TFs encoded by genes regulated through adenine methylation and representing major TF families, representing the most extensive DAP-seq study in filamentous fungi. This analysis reveals their binding profiles and recognized sequences, expanding and diversifying the catalog of known fungal motifs. By integrating this data with DNA 6-methyladenine profiling, we uncover the extensive direct and indirect impact of this epigenetic modification on the regulation of gene expression. Furthermore, the generated data facilitates the identification and functional characterization of TFs involved in biologically relevant processes, such as zinc metabolism and light response, serving as a proof of concept for the utility of the DAP-seq data. These findings not only enhance our understanding of regulatory mechanisms inR. microsporusbut also provide broader insights into gene regulation across the fungal kingdom.
Blue Light Sonata: Dynamic variation of red:blue ratio during the photoperiod differentially affects leaf photosynthesis, pigments, and growth in lettuce
Authors: Van Brenk Jordan B , Vanderwolk Kimberly R , Seo Sumin , Choi Young Hae , Marcelis Leo FM , Verdonk Julian C
Published: January 2025

Vertical farming (VF) has unparalleled capacity to highly customize plant growth environments. In VF, red and blue LED lights are predominantly used as the two main wavelengths for photosynthesis. For many plants, red light increases biomass, and blue light can increase nutritional content. Because red light is more cost-and energy-efficient to produce than blue light, refined growth recipes are imperative to mutualistically improve efficiency with crop yield and quality. This study’s aim was to balance lighting energy-use with growth and nutritional quality by using “dynamic lighting” recipes to reduce durations of high-intensity blue light. Lettuce (Lactuca sativaL.) was grown for 21 days at 220 μmol m-2s-1, receiving one of five R:B ratios (R:B100:0, R:B95:5, R:B89:11, R:B50:50, and R:B0:100) for either the whole 18-hour photoperiod (Whole Day), the first six hours of the photoperiod (Morning), or the last six hours of the photoperiod (Evening). Morning and Evening treatments received low blue (R:B89:11) for the remaining 12 hours of the day. The Morning and Evening high blue treatments had greater fresh weight and leaf area than their respective Whole Day treatments, attributed to reduced instantaneous leaf photosynthesis under high blue. High blue reduced photosynthesis during only the six hours of Morning and Evening treatments, compared to the full impact of static high blue for 18-hour Whole Day treatments. Intriguingly, with only six hours of R:B0:100, Morning and Evening treatments had the same high anthocyanin content as lettuce grown for 18 hours under R:B0:100. Therefore, daily blue light fraction can be reduced by using dynamic treatments to more efficiently promote growth and nutritional quality.
Mouse Cortical Cellular Diversification Through Lineage Progression of Radial Glia
Authors: Yang Lin , Gao Yanjing , Wang Ziwu , Li Zhenmeiyu , Liu Guoping , Xu Zhejun , Zhang Zhuangzhi , You Yan , Yang Zhengang , Li Xiaosu
Published: January 2025

Cortical radial glia (RGs) sequentially generate pyramidal neurons (PyNs) and glia. In this study, we investigated the molecular logic underlying cortical cellular diversification using time-series scRNA-seq and snATAC-seq on FlashTag- or hGFAP-GFP-labeled mouse cortical progenitors across embryonic and postnatal stages. Our data revealed that RGs transition from early to late over time, sequentially producing intermediate neuronal progenitors (INPs) and intermediate glial progenitors (IGPs). While INPs expand exclusively to generate PyNs, IGPs progress from young to old, sequentially producing cortical astrocytes, oligodendrocytes, and olfactory bulb interneurons. We constructed comprehensive molecular maps that reflect cell lineage progression. Our study reveals that chromatin accessibility drives cellular diversification by restricting broadly expressed transcription factors to specific stages and cell types. For instance,Lhx2, which is constantly expressed in RGs across all stages, exhibits reduced DNA-binding activity as development progresses.Lhx2maintains neurogenic competence by establishing an active epigenetic state at neurogenic genes. As RGs transition to later stages, the chromatin regions bound by Lhx2 become inaccessible, leading to the loss of neurogenic competence and the acquisition of gliogenic competence.
A comprehensive molecular atlas of the cell types in the mouse liver
Authors: Pietilä Riikka , Genové Guillem , Mocci Giuseppe , Miao Yuyang , Liu Jianping , Leptidis Stefanos , Del Gaudio Francesca , Uhrbom Martin , Vázquez-Liébanas Elisa , Gustafsson Sonja , Buyandelger Byambajav , Raschperger Elisabeth , Björkegren Johan LM. , Hansson Emil M. , Gaengel Konstantin , Mäe Maarja Andaloussi , Jeansson Marie , Vanlandewijck Michael , He Liqun , Strell Carina , Peng Xiao-Rong , Lendahl Urban , Betsholtz Christer , Muhl Lars
Published: January 2025

The liver plays a crucial role in essential physiological processes, and its impaired function due to liver fibrosis from various causes is an increasingly significant health issue. The liver’s functionality relies on the precise arrangement of its cellular structures, yet the molecular architecture of these units remains only partially understood. We created a comprehensive molecular atlas detailing all the major cell types present in the adult mouse liver through deep single-cell RNA sequencing. Our analysis offers new insights into hepatic endothelial and mesenchymal cells, specifically highlighting the differences between the cells of the periportal microvasculature, the sinusoids, and the portal vein, the latter exhibiting a mixed arterio-venous phenotype. We identified distinct subpopulations of hepatic stellate cells, fibroblasts, and vascular mural cells located in different anatomical regions. Comparisons with transcriptomic data from disease models indicate that a previously unrecognized capsular population of hepatic stellate cells expands in response to fibrotic disease. Our findings reveal that various fibroblast subpopulations respond differently to pathological insults. This data resource will be invaluable for advancing therapeutic interventions targeting hepatic diseases.
Comprehensive Mapping of Human dsRNAome Reveals Conservation, Neuronal Enrichment, and Intermolecular Interactions
Authors: Andrews Ryan J. , Bass Brenda L.
Published: January 2025

The human transcriptome contains millions of A-to-I editing sites arising from an unclear number of poorly characterized dsRNAs. Editing sites are often used to infer presence of dsRNA, but this method is limited by transcription levels, read depth, ADAR expression and cannot identify unedited dsRNA. To address these limitations, we developed dsRNAscan. Applying dsRNAscan to the human genome predicted 5 million dsRNAs. Genomic distribution of dsRNAs encompassing repetitive elements was widespread, but non-repetitive dsRNAs were sparse and enriched at chromosomal tips. dsRNAscan predicted hundreds of long, highly paired dsRNAs suspected to be immunogenic, but only one was in a 3′UTR, and thus likely to challenge cytoplasmic immune sensors. We observed several thousand editing enriched regions suspected to arise from intermolecular structures, and dozens of neuronally enriched dsRNAs conserved across vertebrates. This study offers the first comprehensive set of dsRNA annotations for the human genome, available as a resource athttps://dsrna.chpc.utah.edu/.
Genome assembly ofBougainvilliacf.muscus(Cnidaria: Hydrozoa)
Authors: Macias-Muñoz Aide , Varney Rebecca , Katcher Eva , Everhart Maia , Oakley Todd H.
Published: January 2025

Background

As one of just a handful of non-Bilaterian animal phyla, Cnidaria are key to understanding genome evolution across Metazoa. Despite their importance and diversity, the genomes of most species in the phylum are unsequenced, due in large part to difficulties cultivating them in a laboratory. Here, we present a genome sequence ofBougainvilliacf.mucus, a hydrozoan with four marginal bulbs each containing seven simple eyes (ocelli). This species appeared in our tanks from contamination. While we lacked sufficient samples for transcriptomic or functional studies, we were able to expand our knowledge of how the genome of this species compares to the few, better studied members of hydrozoans by investigating synteny to other cnidarians, repetitive element content, and phylogenetics and synteny of vision-related genes in this eyed species compared to eyeless relatives.

Results

The genome sequence consists of 350 contigs with an N50 of 10 Mb, a total genome length of 375.328 Mb, a BUSCO score of 90.1%, and predicted protein coding genes totaling 46,431. We found a high degree of macrosynteny conservation withHydra vulgarisandHydractinia symbiolongicarpus. Repetitive elements make up 62% of thisBougainvilliagenome. For vision-related genes, we identified 20 cnidarian opsins (cnidops) inBougainvilliaand found instances of gene duplication and loss in families associated with bilaterian eye development, phototransduction, and visual cycling.

Conclusions

This high-quality, contiguous genome in an eyed Hydrozoan will be a valuable resource for additional comparative genomic studies.
Decoding Demosponge Diversity: Bayesian Analysis of Biodiversity, Extinction Events and Environmental Influences throughout the Phanerozoic
Authors: Schuster Astrid , Canfield Donald E.
Published: January 2025

Sponges (phylum Porifera) have been essential to marine ecosystems for over 600 million years, contributing to nutrient cycling, reef building, and ecological stability. Despite their evolutionary importance, the drivers of their diversity dynamics remain poorly understood. This study investigates the diversification patterns of Demospongiae, the largest class of sponges with a well-documented fossil record throughout the Phanerozoic Eon (541–0 Ma). Using fossil occurrence data and a Bayesian framework, we modeled origination and extinction rates to understand their evolutionary history.

Our findings reveal key extinction events, including three previously unrecognized events in the Cambrian, Late Silurian, and Late Jurassic, alongside known events such as the Permian-Triassic and Triassic-Jurassic extinctions. Notably, there was no statistical evidence for mass extinction during the Late Ordovician or Late Devonian. Additionally, Demosponges underwent a significant decline prior to the Cretaceous-Paleogene extinction.

To explore abiotic influences, we applied the Multivariate Birth-Death (MBD) model across all extinction events. This analysis identified correlations between major speciation and extinction events and key variables, including temperature, continental fragmentation, oxygen levels, and sea level, as well as geochemical proxies such as sulfur and strontium, which may reflect underlying drivers like anoxia, weathering, or tectonic activity. Temperature and oxygen levels, in particular, correlated with speciation and extinction during the Permian-Triassic extinction.

These findings underscore the role of environmental fluctuations in shaping demosponge diversity and highlight the complex interplay between changes in abiotic factors and sponge evolution. Our work provides critical insights into the factors driving sponge biodiversity and offers perspectives on how modern sponges might respond to ongoing climate change.

Significance Statement

Sponges are ancient and ecologically pivotal marine organisms that have persisted through Earth’s major environmental upheavals. Despite their resilience, the mechanisms driving their evolutionary responses to past climate shifts remain unclear. By leveraging the fossil record of Demospongiae, this study identifies previously unrecognized extinction events and elucidates how abiotic factors, including temperature and oxygen levels, shaped their diversity during these crises. These findings enhance our understanding of sponge evolutionary dynamics and resilience, offering critical insights into the vulnerability of marine ecosystems under current and future climate change scenarios.
DUSP11 is an intracellular innate immune checkpoint in lung adenocarcinoma
Authors: Thomas Brian J , Bai Xue , Cryer Benjamin J , Escobar Sydney M , Allen Lee-Ann H , Daniels Mark A , Lange Margaret J , Burke-Aguero Donald H
Published: January 2025

The discovery of immune checkpoints and the rapid growth of immuno-oncology (IO) have sparked tremendous efforts to utilize the immune system to treat a wide range of cancer types/subtypes. While the major focus of IO over the past decades has been to manipulate the adaptive immune system, recent attention has been given to manipulating the innate immune system to treat cancer and/or to enhance adaptive responses. In this work we detail the intracellular protein, Dual Specificity Phosphatase 11 (DUSP11), as an innate immune checkpoint (iIC) in Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma (LUAD). Expression of this atypical phosphatase is correlated with patient survival for multiple cancer types, and we show here that its activity is important for the viability of lung cancer cells in vitro. Specifically, we demonstrate that DUSP11 knockdown in LUAD cells induces apoptosis and an innate immune response capable of activating other cells in vitro, and we provide evidence that these phenotypes are primarily mediated by the pattern recognition receptor, retinoic acid inducible gene I (RIG-I). Finally, we show that expression of DUSP11 is important for tumor engraftment and growth of human LUAD in mice. Overall, these data are the first to establish DUSP11 as an immunosuppressive, pro-neoplastic, and potentially targetable protein in LUAD. In addition, our data suggests that the anti-cancer mechanisms induced by diminishing the activity of DUSP11 are likely to be generalizable to other cancer types such as breast cancer, warranting future investigation and therapeutic development.