bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent early-stage squamous cell carcinoma cervical cancer presenting with isolated ovary metastasis: a rare case report
Authors: Le Chinh Tri , Nguyen Anh Quang , Thi Pham Ha Dieu , Tran Long Thanh , Van Truong Hop , Nguyen Dat Ba , Tran Hoang Viet , Nguyen Duc Dinh
Published: September 2023

Introduction:

Ovarian metastatic squamous carcinoma of the cervix is rare, accounting for about 0.4%. This study reports a single case of metastatic recurrent cervical cancer in the ovary.

Case presentation:

A 46-year-old patient with a history of cervical cancer T1b2N0M0 underwent a radical hysterectomy, bilateral pelvic lymph node dissection, and ovarian preservation. One year later, the patient was admitted to the hospital because of abdominal pain in the left iliac fossa; the abdominal computed tomography image showed a left ovarian tumour. The patient underwent laparoscopic left oophorectomy. Postoperative histopathology confirmed ovarian squamous cell carcinoma. From this case, we would like to review the literature on epidemiology, diagnosis, treatment, and prognosis.

Clinical discussion:

Ovarian preservation during surgery in patients with cervical cancer offers many benefits, but careful patient selection is required. However, it should be selected carefully and closely monitored.

Conclusions:

Clinicians should be aware of this situation of ovarian metastasis in patients with early cervical cancer undergoing ovarian-conserving surgery.
Gossypiboma left behind in a cesarean section ended up with a failed laparotomic excision, which demanded another laparotomy to remove it: a rare case report
Authors: Abdullah Lava , Alsulaiman Sihaam Saleh , Imran Muhammad , Barakat Rafe , Rustum Osama
Published: September 2023

Introduction and importance:

Retained surgical items are an uncommon complication for surgical operations, with an estimated incidence of 1 in 5500 to 1 in 18 000 operations. Retained surgical sponges are the most common retained surgical items, accounting for nearly 70%. In 1884, Wilson reported the first retained foreign body after laparotomy.

Case presentation:

A 22-year-old woman was referred to our hospital complaining of a feeling of abdominal bloating and heaviness associated with pain, fever, fatigue, and severe stink vaginal discharges. Past surgical history included a cesarean section followed by laparotomy to remove a foreign body left behind; the obstetrician denied the presence of any foreign body. The diagnosis of retained surgical sponges was done in our hospital, according to the clinical history and radiographic study. The second laparotomy was performed, and the surgical sponge was removed.

Clinical discussion:

Retained surgical items' symptoms vary according to the site and types of materials. The diagnosis may be difficult because it resembles benign or malignant soft-tissue tumors of the abdomen and pelvis. Ultrasound and computed tomography have been used for the diagnosis of retained surgical items. The minimally invasive surgical approach appears to be most successful if the object is located early in the postoperative course.

Conclusion:

Retained surgical items are serious problems of surgical operations and should be among the differential diagnosis of any abdominal pain in patients with a history of prior surgery.
Sacral agenesis without maternal diabetes: a case report
Authors: Thapa Jagadish , Pandey Abhishek , Pandey Archana , Keshari Suraj , Bista Karuna , Chaudhary Aashutosh
Published: September 2023

Introduction:

Sacral agenesis is a rare congenital condition that is characterized by sacrococcygeal bone agenesis. It is associated with spinal cord anomalies as well as problems with the genitourinary system, large bowel, and lower extremities. Fetal ultrasound allows for diagnosis even before birth.

Case presentation:

The authors present the case of a 1-year-old girl with sacral agenesis type III and bilateral congenital talipes equinovarus with spina bifida who was born to a nondiabetic mother and had a normal anomaly scan.

Clinical discussion:

People with less severe forms of sacral agenesis can live a normal life, and it is not connected with cognitive impairment; however, concomitant bladder, colon, and lower limb disorders cause considerable morbidity. The majority of treatment is supportive, frequently requiring orthopedic, urological, gastroenterological, pediatric, and physiotherapy support.

Conclusion:

Genetic and prepregnancy counseling, as well as early screening of high-risk mothers, remain the only options for prevention of the disease since treatment is mostly supportive.
De novo subgaleal abscess complicated by spontaneous osteomyelitis and epidural abscess: a case report and review of literature
Authors: Timilsina Binita , Suryabanshi Anil , Adhikari Niranjan , Luitel Prajjwol , Paudel Sujan , Thapa Bikash , Sharma Mohan R.
Published: September 2023

Introduction and importance:

A subgaleal abscess is a collection of pus in a potential space between the galea aponeurotica and pericranium. De novo subgaleal abscesses are a subset of subgaleal abscesses that develop in the absence of identifiable risk factors such as head trauma or procedures. However, these have rarely been reported in the literature.

Case presentation:

We present the case of a 65-year-old woman who presented with a headache for two and a half months, followed by swelling of the right parieto-occipital scalp. She denied any history of trauma, procedures, or anticoagulant use. A diagnosis of subgaleal abscess complicated by osteomyelitis and epidural abscess was made after obtaining a computed tomography of the head. Surgical treatment consisting of drainage, debridement, and craniectomy was performed, and the disease was successfully treated with a 6-week course of antibiotics.

Clinical discussion:

It is uncommon to have a de novo subgaleal abscess with spontaneous osteomyelitis and an epidural abscess as concurrent complications. The symptoms can be subtle, such as chronic headaches which can lead to delayed hospital visits. Computed tomography of the head is sufficient to make a definitive diagnosis. Appropriate antibiotic therapy and surgical intervention are necessary, which may encompass incision, drainage, debridement, and occasionally a craniectomy in order to achieve full resolution.

Conclusions:

One should be vigilant when evaluating scalp swelling for possible underlying abscesses. Prompt diagnosis and appropriate surgical treatment with adequate antibiotics are preferred treatment options for de novo subgaleal abscesses.
The Role of Additional Staining in the Assessment of the Peritoneal Regression Grading Score (PRGS) in Peritoneal Metastasis of Gastric Origin
Authors: Solass Wiebke , Nadiradze Giorgi , Reymond Marc A. , Bösmüller Hans
Published: September 2023

Introduction:

The Peritoneal Regression Grading Score (PRGS) is a 4-tied histologic regression grading score for determining the response of peritoneal metastasis to chemotherapy. Peritoneal biopsies in every abdominal quadrant are recommended. A positive therapy response is defined as a decreasing or stable mean PRGS between 2 therapy cycles. The added value of periodic acid satin (PAS) and Ber-EP4 staining over HE staining for diagnosing PRGS1 (the absence of vital tumor cells) is unclear.

Materials and Methods:

A total of 339 biopsies obtained during 76 laparoscopies in 33 patients with peritoneal metastasis of gastric cancer were analyzed. Biopsies classified as PRGS 1 (no residual tumor, n=95) or indefinite (n=50) were stained with PAS, and remaining indefinite or PRGS1 cases additionally stained with BerEP4.

Results:

After PAS-staining tumor cells were detected in 28 out of 145 biopsies (19%), the remaining 117 biopsies were immunostained with Ber-EP4. Tumor cells were detected in 22 biopsies (19%). In total, additional staining allowed the detection of residual tumor cells in 50 out of 339 biopsies (15%) and changed the therapy response assessment in 7 out of 33 (21%) patients.

Conclusions:

In summary, 25% (24 out of 95) of initially tumor-free samples (PRGS1) showed residual tumor cells after additional staining with PAS and/or BerEp4. Immunohistochemistry provided important additional information (the presence of tumor cells) in 22 of all 339 biopsies (11.2%). Further staining reduced the instances of unclear diagnosis from 50 to 0 and changed the therapy response assessment in 7 out of 33 patients (21%). We recommend additional staining in PRGS1 or unclear cases.
Systematic review of topical interventions for the management of pain in chronic wounds
Authors: Ffrench Cathal , Finn David , Velligna Akke , Ivory John , Healy Catherine , Butler Karen , Sezgin Duygu , Carr Peter , Probst Sebastian , McLoughlin Aonghus , Arshad Sundus , McIntosh Caroline , Gethin Georgina
Published: September 2023

Chronic wounds adversely affect quality of life. Pain is associated with chronic wounds, and its impact can vary according to wound aetiology, condition, and patient factors. This systematic review examined the effectiveness of topical interventions in the management chronic wound–related pain guided by PRISMA recommendations of randomised controlled trials (RCTs) where pain reduction is the primary outcome. Inclusion criteria were adults (older than 18 years) with chronic venous, arterial, diabetic, or pressure ulcers where pain has been managed through topical administration of pharmacological/nonpharmacological agents. Searches were conducted in Ovid Embase, Ovid MEDLINE, EBSCOhost, CINAHL, CENTRAL, PubMed, Web of Science, and Scopus. Studies were screened for eligibility; risk of bias and data were extracted by 2 independent assessors. Searches retrieved 10,327 titles and abstracts (7760 after deduplication). Nine full texts (1323 participants) examining ibuprofen (n = 4), morphine (n = 2), BWD + PHMB [polihexanide-containing biocellulose wound dressing] (n = 1), and EMLA (n = 2) were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Meta-analysis was not possible, but initial exploration suggests improved outcomes (reduced pain) for ibuprofen when compared with controls. Two studies involving morphine showed conflicting findings. Included studies often had small samples, and considering confounding factors (eg, comorbidities), the results should be interpreted with caution. Review of included studies suggests that topical interventions may provide pain relief in individuals with chronic wounds. Further adequately powered RCTs are recommended to assess the efficacy of topical interventions for the management of chronic wound–related pain.
Categorizing Patient Selection, Outcomes, and Indications in a Decade of 405 Profunda Artery Perforator Flaps
Authors: Haddock Nicholas T. , Lakatta Alexis C. , Teotia Sumeet S.
Published: September 2023

Background:

Autologous tissue is the only permanent option for breast reconstruction. Whereas abdominal tissue remains popular, considering alternative donor sites ensures comprehensive care tailored to a patient. The thigh has been established as an excellent choice in autologous reconstruction. The authors present a 10-year experience with 405 profunda artery perforator (PAP) flaps.

Methods:

An institutional review board–approved 10-year retrospective review of all patients treated with PAP flaps for breast reconstruction was performed. Procedures were carried out by 2 surgeons at the same institution. PAP flaps were divided into 4 consecutive groups with approximately 100 flaps in each group. Demographics, indications, intraoperative data, postoperative complications, revisions, and patient-reported outcomes were recorded and analyzed.

Results:

A total of 207 patients (405 PAP flaps) were included. This accounted for 17.2% of all breast reconstruction flaps. A total of 55% of patients underwent a multiflap procedure. The average flap weight was 354.3 g (±117.2), which decreased significantly over time (P < 0.001). Rates of major complications were 9.6% wounds, 4.4% seromas, 4.7% hematomas, and 3.5% infections. Total flap loss was 2%, 67% of which were in stacked cases. Satisfaction routinely improved from before to after surgery.

Conclusions:

As available flap donor sites continue to evolve, tailoring breast reconstruction to the individual patient is standard in centers of excellence. The PAP flap has emerged as an excellent choice for autologous-based breast reconstruction through use of proper patient selection and surgical technique.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Use of Thromboprophylaxis after Autologous Breast Reconstruction: A Cost-Effective Break-Even Analysis
Authors: Lee Charles C. , Lo Alexis , Lorenz F. Jeffrey , Martinazzi Brandon J. , Johnson T. Shane
Published: September 2023

Background:

Postoperative venous thromboembolism (VTE) is a major source of morbidity and mortality. The use of thromboprophylaxis among surgeons is not well studied in autologous breast reconstruction. The purpose of this study was to determine the rate of VTE in patients with breast cancer undergoing autologous breast reconstruction and to compare the cost-effectiveness of postoperative chemoprophylactic agents.

Methods:

The TriNetX National Health Research Network database was used to identify patients with breast cancer who underwent autologous breast reconstruction surgery between 2002 and 2022. The incidence of VTE within the first 30 days of surgery was calculated. A break-even analysis was performed to determine the break-even rate of VTE at which a chemoprophylactic agent would be cost-effective.

Results:

A cohort of 8221 patients was identified in this study. The rate of VTE was significantly higher in those without anticoagulation (4.0%) compared with those who received anticoagulation (2.6%) (P = 0.0008). The break-even analysis for heparin and enoxaparin cost-effectiveness yielded absolute risk reductions of 0.73% and 1.63% for high-risk patients requiring 30 days of therapy and 0.20% and 0.43% for moderate-risk patients requiring 7 days of therapy, respectively.

Conclusions:

The use of thromboprophylaxis significantly lowered the risk of VTE within 30 days after autologous breast reconstruction. Heparin appeared to be more cost-effective at preventing VTE compared with enoxaparin for both high- and moderate-risk patients. The presented model holds potential for other institution-specific variables that can be easily applied by plastic surgeons to determine the cost-effectiveness of any therapy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Contemporary management of common bile duct stone: What you need to know
Authors: Hwang Franchesca , Bukur Marko
Published: September 2023

Choledocholithiasis is a common presentation of symptomatic cholelithiasis encountered by the acute care surgeon. There is a wide spectrum of variation in management of this disease due to evolutions in laparoscopic and endoscopic techniques. Intricacies in management are related to the timing of diagnosis as well as locally available imaging modalities, surgical expertise, and ancillary advanced endoscopy and interventional radiological support. While individual patient demographics and institutional characteristics will determine management of choledocholithiasis, it is incumbent for the treating surgeon to be well versed in all manners of therapy currently available. The objective of this review is to provide an evidence-based summary of the contemporary management of choledocholithiasis.
Better late than never—a single-center review of delayed rib fixation for symptomatic rib fractures and nonunions
Authors: Bauman Zachary M. , Khan Hason , Cavlovic Lindsey , Todd Sydney , Cemaj Samuel , Daubert Trevor , Raposo-Hadley Ashley , Matos Miguel , Sheppard Olabisi , Berning Bennett , Kamien Andrew , Evans Charity H. , Cantrell Emily
Published: September 2023

BACKGROUND

Surgical stabilization of rib fractures (SSRFs) has become an emerging therapy for treatment of patients with rib fractures. More commonly, it is used in the acute setting; however, delayed SSRF can be utilized for symptomatic rib fracture nonunions. Here, we describe our institution's experience with delayed SSRF, hypothesizing it is safe and resolves patient symptoms.

METHODS

This is a retrospective review of patients presenting to our Level I trauma center to undergo delayed SSRF for symptomatic nonunions from January 2017 to September 2022. Delayed SSRF was defined as SSRF over 2 weeks in the outpatient setting. Basic demographics were obtained. Outcomes of interest included mean pain score (preoperatively and postoperatively), intensive care unit (ICU) and hospital length of stay (LOS), and resolution of preoperative symptoms, specifically chest wall instability, with return to activities of daily living (ADLs).

RESULTS

Forty-four patients met inclusion criteria with a total of 156 symptomatic nonunion rib fractures that received delayed SSRF. The average age was 59.2 ± 11.9 years and median number of days from injury to SSRF was 172.5 (interquartile range, 27.5–200). The average number rib fractures plated per patient 3.5 ± 1.8. Only three patients required ICU admission postoperatively for no longer than 2 days. Median hospital LOS was 2 days (interquartile range 1–3 days). Average preoperative and postoperative pain score was 6.8 ± 1.9 and 2.02 ± 1.5, respectively (p < 0.001). Chest wall instability and preoperative symptoms resolved in 93.2% of patients postoperatively (p < 0.001). Two patients (4.5%) had postoperative complications that resolved after additional surgical intervention. Rib fracture healing was demonstrated on radiographic imaging during postoperative follow-up.

CONCLUSION

Delayed SSRF is safe and demonstrates significant resolution of preoperative symptoms by decreasing pain, improving chest wall stability, and allowing patients to return to activities of daily living.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Academic-Practice Partnership to Prevent and Manage Pressure Injuries
Authors: Otts Jo Ann , Pittman Joyce , Riley Bettina , Mestas Lisa , Hall Heather
Published: September 2023

PURPOSE:

This evidence-based quality improvement (EBQI) initiative examined the effect of an academic-practice (A-P) partnership on improvement in quality measures in an acute care setting, specifically hospital-acquired pressure injury (HAPI) prevention and management.

DESIGN:

A pre-/postdescriptive design was conducted using the practice-informed active learning program to guide the project.

PARTICIPANTS AND SETTING:

The EBQI initiative was conducted at a Southern Gulf-Coast university college of nursing and clinical nursing practice leaders at its affiliated 406-bed academic health center/level I trauma center, regional burn center, and comprehensive stroke center. Both institutions are located in the Southeastern United States (Mobile, Alabama).

METHODS:

The A-P council used a participatory action research approach and developed a practice-informed active learning program incorporating Melnyk's evidence-based practice (EBP) steps, the Donabedian Model and the Patient-Centered Outcomes Research Institute (PCORI) Stakeholder Engagement in Question Development and Prioritization (SEED).

METHOD:

Hospital-acquired pressure injuries were selected as the quality outcome to address. To identify HAPI prevention/management evidenced-based practices, the A-P council conducted an integrative literature review and developed a concept map and the Pressure Injury Prevention Gap Analysis Instrument. The gap analysis identified significant gaps between EBP and current pressure injury prevention practices, with priority ranking of gaps for action by key stakeholders.

OUTCOME:

Following the practice-informed active learning program objectives, the A-P council identified 79 HAPI best EBPs organized by Donabedian domains of structure, process, and outcome and prioritized 3 gaps for action. Actions to address the HAPI gaps included: restructuring the hospital HAPI program, incorporating appropriate leadership to guide the HAPI program, modifying the HAPI reporting process, hiring specialized experts (WOC nurses) with emphasis on pressure injury prevention, establishing a standardized HAPI prevalence survey, improving electronic documentation, increasing transparency of HAPI reporting, improving HAPI accountability at the unit level, and exploring technology to enhance skin assessment. While HAPIs increased by 6.3% from 2019 (n = 104) to 2021 (n = 111), HAPI severity (Stages 3 and 4) decreased by 9.9% from 2019 (n = 14, or 13.46%) to 2021 (n = 4, or 3.6%).

IMPLICATIONS FOR PRACTICE:

Our experience with this quality improvement initiative indicates that an A-P partnership can provide a model to address complex clinical problems, quality indicators, and quality improvement while advancing a culture of inquiry and scholarship and building nursing capacity.
Plum modulates Myoglianin and regulates synaptic function in
D. melanogaster
Authors: Sahota Virender K. , Stone Aelfwin , Woodling Nathaniel S. , Spiers Jereme G. , Steinert Joern R. , Partridge Linda , Augustin Hrvoje
Published: September 2023

Alterations in the neuromuscular system underlie several neuromuscular diseases and play critical roles in the development of sarcopenia, the age-related loss of muscle mass and function. Mammalian Myostatin (MST) and GDF11, members of the TGF-β superfamily of growth factors, are powerful regulators of muscle size in both model organisms and humans. Myoglianin (MYO), the
Drosophila
homologue of MST and GDF11, is a strong inhibitor of synaptic function and structure at the neuromuscular junction in flies. Here, we identified Plum, a transmembrane cell surface protein, as a modulator of MYO function in the larval neuromuscular system. Reduction of Plum in the larval body-wall muscles abolishes the previously demonstrated positive effect of attenuated MYO signalling on both muscle size and neuromuscular junction structure and function. In addition, downregulation of
Plum
on its own results in decreased synaptic strength and body weight, classifying Plum as a (novel) regulator of neuromuscular function and body (muscle) size. These findings offer new insights into possible regulatory mechanisms behind ageing- and disease-related neuromuscular dysfunctions in humans and identify potential targets for therapeutic interventions.
Predictors of SARS-CoV-2 anti-Spike IgG antibody levels following two COVID-19 vaccine doses among children and adults in the Canadian CHILD Cohort
Authors: Azeez Rilwan , Lotoski Larisa , Winsor Geoffrey L. , Arnold Corey R. , Galipeau Yannick , Pelchat Martin , Goguen Stephanie , Simons Elinor , Moraes Theo J. , Mandhane Piush J. , Turvey Stuart E. , Bolotin Shelly , Patrick David M. , Bullard Jared , Lix Lisa M. , Doucas Natasha , Rodriguez Natalie , Brinkman Fiona S.L. , Subbarao Padmaja , Langlois Marc-André , Azad Meghan B.
Published: September 2023

Background

Vaccination helps prevent SARS-CoV-2 infection and severe COVID-19. However, vaccine-induced humoral immune responses vary among individuals and wane over time. We aimed to describe the SARS-CoV-2 anti-spike IgG antibody response to vaccination and identify health and demographic factors associated with this response among children and adults.

Methods

We studied a subset of double-vaccinated children (n= 151; mean age: 12 ±1.5 years, 46% female) and adults (n= 995; 44 ±6.0 years, 60% female) from the Canadian CHILD Cohort. Dried blood spots were collected over two time periods (March 2021 to September 2021; October 2021 to January 2022). Antibody levels were quantified using automated chemiluminescent ELISAs. Demographic, vaccination, and health data were collected via online questionnaires. Associations were determined using multivariable regression.

Results

Our cohort had SARS-CoV-2 anti-spike seropositivity rate of 97% following two COVID-19 vaccine doses. In both children and adults, the highest antibody levels were observed around three months post-vaccination and did not differ by biological sex. Higher antibody levels were associated with: prior SARS-CoV-2 infection (β=0.15 scaled luminescence units, 95%CI, 0.06-0.24), age <18 years (β=0.15, 95%CI 0.05-0.26) and receiving the Moderna mRNA (β=0.23, 95%CI 0.11-0.34) or Pfizer-BioNTech mRNA vaccines (β= 0.10, 95%CI, 0.02-0.18) vs. a combination of mRNA and Oxford-AstraZeneca viral vector vaccines. There were no differences in antibody levels when comparing a 3-8 vs. 9-16-week interval between vaccine doses.

Interpretation

We identified key factors associated with post-vaccination antibody responses in children and adults, which could help improve future vaccine development and deployment among different population subgroups.
Prediction of mycotoxin response of DNA-wrapped nanotube sensor with machine learning
Authors: Rabbani Y. , Behjati S. , Lambert B. P. , Sajjadi S. H. , Shariaty-Niassar M. , Boghossian A. A.
Published: September 2023

DNA-wrapped single-walled carbon nanotubes (DNA-SWCNTs) have demonstrated great versatility as optical sensors. SWCNTs emit a near-infrared fluorescence that is responsive to the slightest changes in their environment, enabling the creation of sensors that can respond to single-molecule fluctuations within the vicinity of their surfaces. The fluorescence response and surface interactions of these sensors are determined by the DNA wrapping sequence. However, the lack of information on the relationship between the DNA sequence and its effect on the SWCNT fluorescence remains a bottleneck for designing sensors specific to analytes of interest. The use of directed evolution was recently demonstrated in order to evolve SWCNT sensors towards mycotoxins through iterative cycles of DNA mutation, screening and selection. In the current work, we use the data acquired during the directed evolution of DNA-SWCNT sensors to train machine learning (ML) algorithms. Artificial neural network (ANN) and support vector machine (SVM) methods were used to predict the response of DNA-SWCNT sensors to the mycotoxin. The reliability of the models was assessed through cross-validation. The cross-validated ANN and SVM models were able to accurately classify the various DNA-SWCNTs as yielding either a high or low fluorescence response with an accuracy of 73 and 81%, respectively. The models were further tested on alternative similar and dissimilar DNA sequences outside of the initial training dataset. The ANN model showed a better ability to predict dissimilar DNA sequences resulting in a high sensor response in comparison with the SVM model. In addition, the possibility to combine the two SVM and ANN models with directed evolution methods was investigated. The experimental results showed that the SVM model was able to predict the response of DNA-SWCNT sensors with 95% accuracy. Finally, the Hierarchy and k-means++ clustering methods were used to examine the similarity and dissimilarity of each DNA sequence at every stage of our investigation. In this work, we show that the application of ML algorithms to directed evolution libraries of DNA allows one to accurately map the performances of DNA-SWCNT sensors within a particular DNA sequence space. Moreover, the computational success of this mapping provides a framework for replacing current empirical approaches with the rational design of DNA sequences for SWCNT sensing.
Combining environmental DNA and remote sensing for efficient, fine-scale mapping of arthropod biodiversity
Authors: Li Yuanheng , Devenish Christian , Tosa Marie I. , Luo Mingjie , Bell David M. , Lesmeister Damon B. , Greenfield Paul , Pichler Maximilian , Levi Taal , Yu Douglas W.
Published: September 2023

Arthropods contribute importantly to ecosystem functioning but remain understudied. This undermines the validity of conservation decisions. Modern methods are now making arthropods easier to study, since arthropods can be mass-trapped, mass-identified, and semi-mass-quantified into ‘many-row (observation), many-column (species)’ datasets, with homogeneous error, high resolution, and copious environmental-covariate information. These ‘novel community datasets’ let us efficiently generate information on arthropod species distributions, conservation values, uncertainty, and the magnitude and direction of human impacts. We use a DNA-based method (barcode mapping) to produce an arthropod-community dataset from 121 Malaise-trap samples, and combine it with 29 remote-imagery layers within a joint species distribution model. With this approach, we generate distribution maps for 76 arthro-pod species across a 225 km2temperate-zone forested landscape. We combine the maps to visualise the fine-scale spatial distributions of species richness, community composition, and site irreplaceability. Old-growth forests show distinct community composition and higher species richness, and stream courses have the highest site-irreplaceability values. With this ‘sideways biodiversity modelling’ method, we demonstrate the feasibility of biodiversity mapping at sufficient spatial resolution to inform local management choices, while also being efficient enough to scale up to thousands of square kilometres.
Subchronic exposure to ambient PM2.5impairs novelty recognition and spatial memory
Authors: Kim Sun-Hong , Das Darpan , Sillé Fenna C. M. , Ramachandran Gurumurthy , Biswal Shyam
Published: September 2023

Air pollution remains a great challenge for public health, with the detrimental effects of air pollution on cardiovascular, rhinosinusitis, and pulmonary health increasingly well understood. Recent epidemiological associations point to the adverse effects of air pollution on cognitive decline and neurodegenerative diseases. Mouse models of subchronic exposure to PM2.5(ambient air particulate matter < 2.5 µm) provide an opportunity to demonstrate the causality of target diseases. Here, we subchronically exposed mice to concentrated ambient PM2.5for 7 weeks (5 days/week; 8h/day) and assessed its effect on behavior using standard tests measuring cognition or anxiety-like behaviors. Average daily PM2.5concentration was 200 µg/m3in the PM2.5group and 10 µg/m3in the filtered air group. The novel object recognition (NOR) test was used to assess the effect of PM2.5exposure on recognition memory. The increase in exploration time for a novel object versus a familiarized object was lower for PM2.5-exposed mice (42% increase) compared to the filtered air (FA) control group (110% increase). In addition, the calculated discrimination index for novel object recognition was significantly higher in FA mice (67 %) compared to PM2.5exposed mice (57.3%). The object location test (OLT) was used to examine the effect of PM2.5exposure on spatial memory. In contrast to the FA-exposed control mice, the PM2.5exposed mice exhibited no significant increase in their exploration time between novel location versus familiarized location indicating their deficit in spatial memory. Furthermore, the discrimination index for novel location was significantly higher in FA mice (62.6%) compared to PM2.5exposed mice (51%). Overall, our results demonstrate that subchronic exposure to higher levels of PM2.5in mice causes impairment of novelty recognition and spatial memory.
The effect of lactational low protein diet on skeletal muscle during adulthood and ageing in male and female mouse offspring
Authors: Alameddine Moussira , Altinpinar Atilla Emre , Ersoy Ufuk , Kanakis Ioannis , Myrtziou-Kanaki Ioanna , Ozanne Susan E , Goljanek-Whysall Katarzyna , Vasilaki Aphrodite
Published: September 2023

Sarcopenia is characterised by loss of skeletal muscle mass and function associated with a reduction in muscle fibres. External factors, like exercise and diet, can also influence skeletal muscle mass and contribute to muscle fibre loss. Maternal programming refers to the effect of maternal environmental factors such as nutrition that lead to phenotypic changes in the offspring. Maternal malnutrition has been linked to a reduction in body weight and impaired development of skeletal muscle of the offspring; however, there are no studies that reported the long-term effect of maternal low protein diet on the ageing of skeletal muscles. This study aimed to examine how maternal protein deficiency during lactation affects skeletal muscle development and ageing in the offspring. Pups born from normally fed mothers were lactated by low protein fed mothers. Post-weaning, mice were either maintained on a low protein diet (LPD) or switched to normal protein diet (NPD). Pups born from normally fed mothers and maintained on NPD during lactation and afterwards were used as control. In males, the diet mainly affected the size of the myofibres without major effect on fibre number and led to a reduced grip strength of ageing mice (24 months). Female mice had a lower body and muscle weight at weaning but caught up with control mice at 3 months. During ageing, muscle weight, myofibre number and survival rate of female pups were significantly affected. These findings highlight longitudinal animal research for nutritional programming and the importance of sexual dimorphism in response to challenges.

Highlights

Postnatal low protein diet significantly decreases the survival rate of female but not male mice.

During ageing, female mice fed a low protein diet during lactation have lower muscle weight.

During ageing, female mice fed a low protein diet postnatally maintain their myofibre number.

Male mice fed a low protein diet postnatally have lower body weight and muscle weight throughout their lifespan.

Low protein diet affects myofibres size ofTAmuscle of male but not female mice at 3 months of age however this effect is lost during ageing.
Spatiospectral image processing workflow considerations for advanced MR spectroscopy of the brain
Authors: Cai Leon Y. , Del Tufo Stephanie N. , Barquero Laura , D’Archangel Micah , Sachs Lanier , Cutting Laurie E. , Glaser Nicole , Ghetti Simona , Jaser Sarah S. , Anderson Adam W. , Jordan Lori C. , Landman Bennett A.
Published: September 2023

Magnetic resonance spectroscopy (MRS) is one of the few non-invasive imaging modalities capable of making neurochemical and metabolic measurementsin vivo. Traditionally, the clinical utility of MRS has been narrow. The most common use has been the “single-voxel spectroscopy” variant to discern the presence of a lactate peak in the spectra in one location in the brain, typically to evaluate for ischemia in neonates. Thus, the reduction of rich spectral data to a binary variable has not classically necessitated much signal processing. However, scanners have become more powerful and MRS sequences more advanced, increasing data complexity and adding 2 to 3 spatial dimensions in addition to the spectral one. The result is a spatially- and spectrally-variant MRS image ripe for image processing innovation. Despite this potential, the logistics for robustly accessing and manipulating MRS data across different scanners, data formats, and software standards remain unclear. Thus, as research into MRS advances, there is a clear need to better characterize its image processing considerations to facilitate innovation from scientists and engineers. Building on established neuroimaging standards, we describe a framework for manipulating these images that generalizes to the voxel, spectral, and metabolite level across space and multiple imaging sites while integrating with LCModel, a widely used quantitative MRS peak-fitting platform. In doing so, we provide examples to demonstrate the advantages of such a workflow in relation to recent publications and with new data. Overall, we hope our characterizations will lower the barrier of entry to MRS processing for neuroimaging researchers.
Disentangling sources of clock-like mutations in germline and soma
Authors: Spisak Natanael , de Manuel Marc , Milligan William , Sella Guy , Przeworski Molly
Published: September 2023

The rates of mutations vary across cell types. To identify causes of this variation, mutations are often decomposed into a combination of the single base substitution (SBS) “signatures” observed in germline, soma and tumors, with the idea that each signature corresponds to one or a small number of underlying mutagenic processes. Two such signatures turn out to be ubiquitous across cell types: SBS signature 1, which consists primarily of transitions at methylated CpG sites caused by spontaneous deamination, and the more diffuse SBS signature 5, which is of unknown etiology. In cancers, the number of mutations attributed to these two signatures accumulates linearly with age of diagnosis, and thus the signatures have been termed “clock-like.” To better understand this clocklike behavior, we develop a mathematical model that includes DNA replication errors, unrepaired damage, and damage repaired incorrectly. We show that mutational signatures can exhibit clocklike behavior because cell divisions occur at a constant rate and/or because damage rates remain constant over time, and that these distinct sources can be teased apart by comparing cell lineages that divide at different rates. With this goal in mind, we analyze the rate of accumulation of mutations in multiple cell types, including soma as well as male and female germline. We find no detectable increase in SBS signature 1 mutations in neurons and only a very weak increase in mutations assigned to the female germline, but a significant increase with time in rapidly-dividing cells, suggesting that SBS signature 1 is driven by rounds of DNA replication occurring at a relatively fixed rate. In contrast, SBS signature 5 increases with time in all cell types, including post-mitotic ones, indicating that it accumulates independently of cell divisions; this observation points to errors in DNA repair as the key underlying mechanism. Thus, the two “clock-like” signatures observed across cell types likely have distinct origins, one set by rates of cell division, the other by damage rates.
Essential role of an acidic endosomal environment in JAK3-mediated signal transduction
Authors: Amano Yuji , Tanaka Nobuyuki , Takeshita Toshikazu , Kojima Katsuhiko
Published: September 2023

The endosome, an acidic organelle, is a platform for endocytic trafficking and signal transduction. Chloroquine, an intercellular acidic vesicle neutralizer (IAVN), has been used to treat autoimmune diseases. Its immunosuppressive mechanism remains unclear, although several modes of action attributable to lysosomal dysfunction have been postulated. This study found that IAVNs, including chloroquine, can selectively interfere with common cytokine receptor γ chain (γc) cytokine-induced signal transduction. Our data show that JAK3 targets endosomal membranes in an acidic pH-dependent manner, which is essential for γc-cytokine-induced functional signal complex formation and signal activation. Among IAVNs, Monensin and similar ionophores were particularly effective in suppressing γc-cytokine-induced cell proliferation in vitro. Monensin exerted therapeutic effects in a collagen-induced arthritis mouse model by interfering with T helper 17 cells. Our findings help further understand the immunosuppressive mechanism of IAVNs and unveil the spatial regulation of JAK3-mediated signal transduction via endosomes.
Simplicity: web-based visualization and analysis of high-throughput cancer cell line screens
Authors: Ling Alexander L. , Zhang Weijie , Lee Adam , Xia Yunong , Su Mei-Chi , Gruener Robert F. , Jena Sampreeti , Huang Yingbo , Pareek Siddhika , Shan Yuting , Huang R. Stephanie
Published: September 2023

High-throughput drug screens are a powerful tool for cancer drug development. However, the results of such screens are often made available only as raw data, which is intractable for researchers without informatic skills, or as highly processed summary statistics, which can lack essential information for translating screening results into clinically meaningful discoveries. To improve the usability of these datasets, we developed Simplicity, a robust and user-friendly web interface for visualizing, exploring, and summarizing raw and processed data from high-throughput drug screens. Importantly, Simplicity allows for easy recalculation of summary statistics at user-defined drug concentrations. This allows Simplicity’s outputs to be used with methods that rely on statistics being calculated at clinically relevant doses. Simplicity can be freely accessed athttps://oncotherapyinformatics.org/simplicity/.
Benchmarking Hayai-Annotation Plants: A Re-evaluation Using Standard Evaluation Metrics
Authors: Ghelfi Andrea , Shirasawa Kenta , Isobe Sachiko
Published: September 2023

The rapid growth of next-generation sequencing (NGS) technology has led to a surge in the determination of whole genome sequences in plants. This has created a need for functional annotation of newly predicted gene sequences in the assembled genomes. To address this, “Hayai-Annotation Plants” was developed as a gene functional annotation tool for plant species. In this report, we compared Hayai-Annotation Plants with Blast2GO and TRAPID, focusing on the three primary gene-ontology (GO) domains: Biological Process (BP), Molecular Function (MF), and Cellular Component (CC). Using theArabidopsis thalianaGO annotation as a benchmark, we evaluated each tool using two approaches: the area under the precision-recall curve (AUC-PR) and the metrics used at the critical assessment of functional annotation (CAFA). In the latter case, a CAFA-evaluator, was used to determine the F-score, weighted F-score, and S-score for each domain. Hayai-Annotation Plants showed better performances in all three GO domains. Our results thus reaffirm the effectiveness of Hayai-Annotation Plants for functional gene annotation in plant species. In this era of extensive whole genome sequencing, Hayai-Annotation Plants will serve as a valuable tool that facilitates simplified and accurate gene function annotation for numerous users, thereby making a significant contribution to plant research.
Insecticide resistance inAedes aegyptifrom the National Capital Region, Philippines
Authors: Angeles Jason R. , Malijan Richard Paul B. , Apilado Ariza Minelle A. , Ammugauan Mary Ann T. , Salazar Ferdinand V.
Published: September 2023

Background

Human arboviral diseases such as dengue, chikungunya and Zika can be transmitted by the mosquitoAedes aegypti. The insecticide-based vector control strategy is critical in reducing the transmission of theseAedes-borne diseases but is threatened mainly by the emergence of insecticide resistance.

Methodology/Principal Findings

AdultAedes aegyptifrom National Capital Region, Philippines were subjected to bioassay to determine their susceptibility to the diagnostic doses of pyrethroid, organochlorine and organophosphate insecticides following the standard World Health Organization insecticide susceptibility test. This study reports for the first time the existence of insecticide resistance inAe. aegyptifrom the Philippines to pyrethroids and organochlorine. Results from this study showed that most of theAe. aegyptipopulations exhibited phenotypic resistance to the pyrethroids (permethrin and etofenprox) and an organochlorine (DDT) while all populations tested to malathion were still susceptible to this organophosphate. Varying resistance levels to deltamethrin, cyfluthrin and lambdacyhalothrin were also observed in the different mosquito populations.

Conclusions

Insecticide resistance exists in local populations ofAe. aegyptifrom the National Capital Region. This finding should alert public health authorities to consider modifying the existing vector management package for greater control efficacy. Best practices that are proven to prevent and/or delay the development of insecticide resistance such as insecticide rotation should be implemented. Alternative toxicants and chemicals with a different mode of action, such as repellents, should be explored to ensure continuing efficacy of program interventions.

Author summary

The National Capital Region (NCR), Philippines reports the country’s highest dengue incidence. Apart from being populous and the center of economic activity, the local government authorities of this region have undertaken significant vector control efforts devoted to dengue. The use of insecticides to reduce mosquito vector density remains the handiest control method. This scenario necessitated the documentation of the resistance levels, particularly of the most important vectorAedes aegypti. An insect is said to be resistant when the known effective dose of an insecticide can no longer sufficiently kills the same insect population. This study showed thatAe. aegyptipopulation from cities in NCR had developed resistance to commonly used pyrethroids (permethrin, etofenprox) and to an organochlorine (DDT). Highly localized variations of resistance and susceptibility within cities at NCR were recorded against deltamethrin, cyfluthrin and lambdacyhalothrin. This finding should alert public health authorities to consider modifying the existing vector management package for greater control efficacy.
An AI Agent for Fully Automated Multi-omic Analyses
Authors: Zhou Juexiao , Zhang Bin , Chen Xiuying , Li Haoyang , Xu Xiaopeng , Chen Siyuan , He Wenjia , Xu Chencheng , Gao Xin
Published: September 2023

With the fast-growing and evolving omics data, the demand for streamlined and adaptable tools to handle the bioinformatics analysis continues to grow. In response to this need, we introduce Automated Bioinformatics Analysis (AutoBA), an autonomous AI agent designed explicitly for fully automated multi-omic analyses based on large language models. AutoBA simplifies the analytical process by requiring minimal user input while delivering detailed step-by-step plans for various bioinformatics tasks. Through rigorous validation by expert bioinformaticians, AutoBA’s robustness and adaptability are affirmed across a diverse range of omics analysis cases, including whole genome/exome sequencing (WGS/WES), chromatin immunoprecipitation assays with sequencing (ChIP-seq), RNA sequencing (RNA-seq), single-cell RNA-seq, spatial transcriptomics and so on. AutoBA’s unique capacity to self-design analysis processes based on input data variations further underscores its versatility. Compared with online bioinformatic services, AutoBA offers multiple LLM backends, with options for both online and local usage, prioritizing data security and user privacy. Moreover, different from the predefined pipeline, AutoBA has adaptability in sync with emerging bioinformatics tools. Overall, AutoBA represents an advanced and convenient tool, offering robustness and adaptability for conventional multi-omic analyses.
Postnatal intestinal epithelial maturation by LSD1 controls the small intestinal immune cell composition independently from the microbiota
Authors: Díez-Sánchez Alberto , Lindholm Håvard T. , Vornewald Pia M , Ostrop Jenny , Parmar Naveen , Shaw Tovah N. , Martín-Alonso Mara , Oudhoff Menno J.
Published: September 2023

Postnatal development of the gastrointestinal tract involves the establishment of the commensal microbiota, maturation of the intestinal epithelium, and the acquisition of immune tolerance via a balanced immune cell composition. While studies have uncovered an interplay between the commensal microbiota and immune system development, less is known about the role of the maturing epithelium. Here, we comprehensively show that intestinal-epithelial intrinsic expression of lysine-specific demethylase 1A (LSD1) is necessary for the postnatal maturation of intestinal epithelium as well as maintaining this developed epithelial state in adulthood. Although the stool microbiome was altered in animals with an intestinal-epithelial specific deletion ofLsd1, by depleting the microbial component using antibiotics, we found that the cellular state and number of certain immune cell types were dependent on maturation of the epithelium. We found plasma cells, innate lymphoid cells (ILCs), and a specific myeloid population to be depending on epithelial LSD1 expression. We propose that LSD1 controls the expression of epithelial-derived chemokines, such asCxcl16, and this is a mode of action for this epithelial-immune cell interplay. For example, we show that LSD1-mediated epithelial-intrinsic CXCL16 controls the number of local ILC2s but not ILC3s. Together, our findings suggest that the maturing epithelium plays a dominant role in regulating the local immune cell composition, thereby contributing to gut homeostasis.