bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection and Characterization of Endplate Structural Defects on CT
Authors: Lawan Aliyu , Leung Andrew , Leung Stephanie , Faul James , Umoh Joseph U. , Holdsworth David W. , Bryant Dianne M. , Battié Michele C.
Published: January 2024

Study Design.

Diagnostic test study.

Objective.

To determine the reliability and validity or diagnostic accuracy of two previously described endplate structural defect (EPSD) assessment methods.

Summary of Background Data.

Studies of EPSD may further the understanding of pathoanatomic mechanisms underlying back pain. However, clinical imaging methods used to document EPSD have not been validated, leaving uncertainty about what the observations represent.

Materials and Methods.

Using an evaluation manual, 418 endplates on CT sagittal slices obtained from 19 embalmed cadavers (9 men and 10 women, aged 62–91 yr) were independently assessed by two experienced radiologists and a novice for EPSD using the two methods. The corresponding micro-CT (µCT) from the harvested T7-S1 spines were assessed by another independent rater with excellent intra-rater reliability (k=0.96).

Results.

Inter-rater reliability was good for the presence (k=0.60–0.69) and fair for specific phenotypes (k=0.43-0.58) of EPSD. Erosion, for which the Brayda-Bruno classification lacked a category, was mainly (82.8%) classified as wavy/irregular, while many notched defects (n=15, 46.9%) and Schmorl’s nodes (n=45, 79%) were recorded as focal defects using Feng’s classification. When compared to µCT, endplate fractures (n=53) and corner defects (n=28) were routinely missed on CT. Endplates classified as wavy/irregular on CT corresponded to erosion (n=29, 21.2%), jagged defects (n=21, 15.3%), calcification (n=19, 13.9%), and other phenotypes on µCT. Some focal defects on CT represented endplate fractures (n=21, 27.6%) on µCT. Overall, with respect to the presence of an EPSD, there was a sensitivity of 70.9% and a specificity of 79.1% using Feng's method, and 79.5% and 57.5% using Brayda-Bruno's method. Poor to fair inter-rater reliability (k=0.26–0.47) was observed for defect dimensions.

Conclusion.

There was good inter-rater reliability and evidence of criterion validity supporting assessments of EPSD presence using both methods. However, neither method contained all needed EPSD phenotypes for optimal sensitivity, and specific phenotypes were often misclassified.
Infection-related Hospitalizations During Immune Checkpoint Inhibitor Treatment Without Immunosuppressants
Authors: Jeung Ye Sul , Chun June Young , Choi Beom Kyu , Park Seog Yun , Lim Hyun-ju , Park Jong Woong , Han Ji-Youn , Lee Youngjoo
Published: January 2024

Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non–small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea. Subsequently, we evaluated the clinical characteristics and treatment outcomes of selected patients hospitalized for potential infectious disease without immunosuppressive treatment (n=80). Eight cases (3.4%) were identified as bacterial pneumonia (n=5) and cellulitis, inflamed epidermoid cyst, and wound infection (n=1 each). The bacterial pathogens Streptococcus pneumoniae and Haemophilus influenzae were identified in 4 patients with pneumonia. The period between the start of ICI treatment and infection varied between 3 and 189 days (median, 24.5 days). Five (62.5%) patients were infected within a month after ICI treatment initiation. All patients were treated with empirical antibiotics and discharged without complications. The median progression-free and overall survival for ICI treatment was 11.5 and 25.5 months, respectively. Six patients experienced ICI-associated adverse effects postinfection: Herpes zoster infection (n=4) and pneumonitis (n=2). Infectious disease independent of immunosuppression is a rare, but possible event in patients with lung cancer receiving ICI treatment. Clinical awareness would enable prompt diagnosis of primary infection during immunotherapy.
Phalloplasty Flap Salvage Using a Superficial Circumflex Iliac Artery Perforator Propeller Flap
Authors: Rochlin Danielle H. , Lin Walter , Reitz Robert J. , Chen Mang , Buntic Rudy , Watt Andrew , Safa Bauback
Published: January 2024

Background:

Partial phalloplasty flap loss presents an evolving challenge, largely due to the complex demands required for both aesthetics and function. We describe our novel experience using the superficial circumflex iliac perforator (SCIP) propeller flap for neophallus salvage when skin grafting alone provides insufficient soft tissue bulk or coverage.

Methods:

We retrospectively reviewed patients who underwent SCIP propeller flap reconstruction after phalloplasty partial flap loss. After suprafascial dissection, superficial circumflex iliac vessel perforator(s) were isolated toward the femoral origin. The flap was rotated 180 degrees and inset into the ventral or distal neophallus depending on the region of flap loss. If glans reconstruction was required, the flap was tubularized before inset. Division and inset were performed at a second stage, followed by subsequent glansplasty, urethral creation, and/or penile implant placement.

Results:

SCIP propeller flap reconstruction was performed for four patients after one to six debridements at a mean of 6.5 (range 1.0-19.2) months following the initial phalloplasty. Three patients had lost the ventral phallus due to venous insufficiency, arterial insufficiency, and excessive postoperative swelling, respectively. The fourth patient experienced near-total loss of the glans following penile implant insertion. Division and inset was performed at an average of 7.5 (range 5.0-12.0) weeks after SCIP flap. There were no complications related to SCIP flap viability.

Conclusion:

The SCIP propeller flap allows salvage of partial flap loss following phalloplasty by providing thin, pliable soft tissue bulk and skin coverage with minimal donor site morbidity, without the need for microsurgery, allowing progression with subsequent reconstructive stages.
Efficacy and Safety of Solid-state Dual-wavelength Lasers for the Treatment of Moderate-to-severe Inflammatory Acne in Asian Populations
Authors: Lim Joyce Teng-Ee
Published: January 2024

Background:

Standard treatments for moderate-to-severe acne often require oral medications but are not long-lasting or free from side effects. We aimed to evaluate the efficacy and safety of a solid-state dual-wavelength laser for moderate-to-severe inflammatory acne in an Asian population.

Methods:

Forty individuals with moderate-to-severe acne received nightly topical retinoids and two to three weekly treatments with a 1319-nm laser followed by a 589-nm laser (five sessions in total). Patients were evaluated at pretreatment baseline, at monthly intervals, and at 1 month after the last laser for pain, seborrhea, global aesthetic improvements, and satisfaction, using standardized digital photography and global assessment scales. Fifteen patients had an additional evaluation 3 months after the fifth session.

Results:

At 1 month, all patients (n = 40) had improved inflammatory acne counts, with 72.5% having greater than 75% reduction in acne count, 7.5% having 51%–75% reduction, 17.5% having 26%–50% reduction and 2.5% having less than 25% reduction. Moreover, GAS evaluations showed that 62.5% of patients improved to almost clear and 37.5% to mild acne (P = 0.0478), while improvements were sustained in patients with 3-month follow-ups. Erythema (n = 29) improved with 65.5% of affected patients having greater than 75% reduction. Patients (n = 17) with pigmentation experienced lightening, with 52.9% of affected patients having a greater than 75% reduction. With low pain scores (mean 3.68 of 10, median 4 of 10), the treatment was well-tolerated. All patients (n = 40) reported acne improvements with 95% having much improved or very much improved, and 95% either satisfied or very satisfied.

Conclusions:

Dual-wavelength lasers effectively and safely treat moderate-to-severe inflammatory acne with high patient satisfaction. It is ideal for patients who refuse or are contraindicated to oral medications, and patients with acne-associated pigmentation, erythema and seborrhea.
Phase 2, open-label, rollover study of cenicriviroc for liver fibrosis associated with metabolic dysfunction–associated steatohepatitis
Authors: Francque Sven M. , Hodge Alexander , Boursier Jerome , Younes Ziad H. , Rodriguez-Araujo Gerardo , Park Grace S. , Alkhouri Naim , Abdelmalek Manal F.
Published: January 2024

Background:

Cenicriviroc (CVC) is a novel, orally administered antagonist of chemokine receptor types 2/5 that has demonstrated antifibrotic activity in a phase 2b study of patients with NASH. This phase 2, open-label, rollover study investigated the long-term safety and tolerability of CVC in patients with NASH and stage 0–4 liver fibrosis.

Methods:

Eligible patients who completed the phase 2 CENTAUR study or reached a predefined endpoint in the phase 3 AURORA study were rolled over and received open-label CVC 150 mg once daily. Safety assessments were conducted at the start of the study, and patients were seen in the clinic every 3 months until the study sponsor terminated CVC development. Safety endpoints included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, adverse event severity, and clinical laboratory assessments.

Results:

A total of 167 patients were enrolled, with a median treatment duration of 33.6 months. Before study termination, 36 patients (21.6%) prematurely discontinued the study. Treatment-related TEAEs were reported in 28 patients (16.8%). The most common treatment-related TEAEs were 4 cases of diarrhea (2.4%) and 2 cases each (1.2%) of abdominal pain, nausea, alanine aminotransferase increased, aspartate aminotransferase increased, hypertriglyceridemia, myalgia, pruritus, and rash. The majority of these treatment-related events were mild in intensity, and none were life-threatening. There were no clinically meaningful changes in hepatic function, chemistry, or liver parameters from baseline to the end of the study.

Conclusions:

In this rollover study, CVC 150 mg once daily was well tolerated in patients with NASH and stage 0–4 liver fibrosis. No new safety signals were reported, and these data further support the safety and tolerability of CVC.
Granulocyte-monocyte/macrophage apheresis for steroid-nonresponsive or steroid-intolerant severe alcohol-associated hepatitis: A pilot study
Authors: Kasuga Ryosuke , Chu Po-sung , Taniki Nobuhito , Yoshida Aya , Morikawa Rei , Tabuchi Takaya , Noguchi Fumie , Yamataka Karin , Nakadai Yukie , Kondo Mayuko , Ebinuma Hirotoshi , Kanai Takanori , Nakamoto Nobuhiro
Published: January 2024

Background:

Patients with severe alcohol-associated hepatitis (SAH) have a high short-term mortality rate. Unmet needs exist in patients who are refractory to corticosteroids (CS) or are ineligible for early liver transplantation.

Methods:

This was a prospective, open-label, nonrandomized pilot study conducted at a liver transplant center in Tokyo, Japan, starting in October 2015. Lille model and Model for End-stage Liver Disease (MELD) score-defined CS nonresponsive or CS-intolerant patients with SAH who fulfilled the inclusion criteria (leukocytosis over 10,000/μL, etc.) were considered for enrollment. The median duration from admission to enrollment was 23 days (IQR, 14-31 days), after standard of care. Granulocyte-monocyte/macrophage apheresis (GMA) performed with Adacolumn twice per week, up to 10 times per treatment course, was evaluated.

Results:

13 GMA treatments were conducted through December 2021. Maddrey Discriminant Function was 53.2

17.7 at admission. The overall survival rate was 90.9% at 90 and 180 days. MELD scores significantly improved, from median (IQRs) of 23 (20–25) to 15 (13–21) after GMA (p<0.0001). Estimated mortality risks using the Lille model and MELD scores significantly improved from 20.9%±16.5% to 7.4%±7.3% at 2 months and from 30.4%±21.3% to 11.6%±10.8% at 6 months, respectively (both p<0.01), and were internally validated. The cumulative rate of alcohol relapse was 35.9% per year. No severe adverse events were observed. In exploratory analysis, granulocyte colony-stimulating factor levels were significantly correlated with prognostic systems such as MELD-Sodium scores after GMA (correlation coefficient= −0.9943, p<0.0001) but not before GMA (p=0.62).

Conclusions:

Compared to published studies, GMA is associated with a lower-than-expected 90- and 180-day mortality in patients with CS-nonresponsive or CS-intolerant SAH. GMA may meet the needs as a salvage anti-inflammatory therapy for SAH. (Trial registration: UMIN000019351 and jRCTs No.032180221) (274 words).
In Vivo Confocal Microscopy Characterization of Candida parapsilosis Keratitis
Authors: Scotto R. , Forte P. , Macrì A. , Bonzano C. , Traverso C. E.
Published: January 2024

The present clinical case concerns two patients with mycotic keratitis because of Candida parapsilosis in which corneal confocal microscopy presented a characteristic feature of this pathogen. Both described patients used a therapeutic contact lens and administered a therapy with steroid eye drops which are well known predisposing factors for the onset of corneal mycoses. This report can be useful for correctly identifying the pathologic condition and quickly directing the therapy.
Safety and efficacy of extended thrombophilia screening directed venous thromboembolic events (VTE) prophylaxis in live liver donors: do we really need extended thrombophilia screening routinely?
Authors: Dogar Abdul Wahab , Hussain Azhar , Ullah Kaleem , Shams-ud-din  , Ghaffar Abdul , Abbasher Hussien Mohamed Ahmed Khabab , Junaid Tahir Muhammad
Published: January 2024

Background and aims:

The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the safety and efficacy of thrombophilia profile testing directed venous thromboembolic events (VTE) prophylaxis while balancing bleeding risk and the need for routine thrombophilia testing before live liver donation among living donor candidates.

Materials and methods:

Protein S (PS), protein C (PC), anti-thrombin (AT) III, and anti-phospholipid antibody panel (APLA) levels were measured in 567 potential donor candidates. Donors were divided into normal, borderline and high-risk groups based on Caprini score. The safety endpoints were VTE occurrence, bleeding complications or mortality.

Results:

Among 567 donors, 21 (3.7%) were deficient in protein C, and 14 (2.5%) were deficient in anti-thrombin-III. IgM and IgG. Anti-phospholipids antibodies were positive in 2/567 (0.4%) and 2/567 (0.4%), respectively. IgM and IgG lupus anticoagulant antibodies were positive in 3/567 (0.5%) and 3/567 (0.5%), respectively. VTE events, bleeding complications and postoperative living donors liver transplantation-related complications were comparable among the three donor groups (P>0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. The mean length of ICU and total hospital stay were comparable. No donor mortality was observed in all donor groups.

Conclusions:

Due to thrombophilia testing directed VTE prophylaxis, VTE events were comparable in normal, borderline and high-risk thrombophilia donor groups, but more evaluations are required to determine the lower safe levels for various thrombophilia parameters including PC, PS and AT-III before surgery among living donor candidates.
Impact of transesophageal echocardiography dynamic monitoring of left ventricular preload on postoperative gastrointestinal function in colorectal cancer patients undergoing radical surgery
Authors: du Jingjing , Zhang Tianyu , Hao Conghui , Xu Hai , Luan Hengfei , Cheng Zhi , Ding Mengyao
Published: January 2024

Background:

Patients undergoing intestinal tumour surgery are fasted preoperatively for a series of bowel preparations, which makes it difficult to assess the patients’ volume, posing a challenge to intraoperative fluid replacement. Besides, inappropriate fluid therapy can cause organ damage and affect the prognosis of patients, and it increases the burden of patients and has a certain impact on patients and families.

Material and methods:

The authors designed a single-centre, prospective, single-blinded, randomized, parallel-controlled trial. Fifty-four patients undergoing elective radical resection of colorectal cancer were selected and divided into two groups according to whether transesophageal echocardiography (TEE) was used or not during the operation, that is the goal-directed fluid therapy (GDFT) group (group T) guided by TEE and the restrictive fluid therapy group (group C). Fluid replacement was guided according to left ventricular end-diastolic volume index (LVEDVI) in group T and according to restrictive fluid replacement regimen in group C.

Results:

The first postoperative exhaust time and defecation time in group T [(45±21), (53±24) h] were significantly shorter (P<0.05) than those in group C [(63±26), (77±30) h]. There were no significant differences (P>0.05) in liquid intake time and postoperative nausea and vomiting incidences between the two groups. The total intraoperative fluid volume in group T was significantly higher (P<0.05) than that in group C. There was no significant difference (P>0.05) in urine volume between the two groups. There were no significant differences (P>0.05) in lactate content, mean arterial pressure, and heart rate at various time points between the two groups. The length of hospital stay in group C [(18±4) days] was significantly longer (P<0.05) than that in group T [(15±4) days].

Conclusions:

For patients undergoing colorectal cancer surgery, fluid therapy by monitoring LVEDVI resulted in faster recovery of gastrointestinal function and shorter hospital stay.
Ethics
Authors: Fuller Switzer Diane , Knowles Suzan Griffis
Published: January 2024

Ethical dilemmas exist with decision-making regarding resource allocations, such as critical care, ventilators and other critical equipment, and pharmaceuticals during pandemics. Triage artificial intelligence (AI) algorithms based on prognostication tools exist to guide these decisions; however, implicit bias may affect the decision-making process leading to deviation from the algorithm recommendations. Conflict within the ethical domain may be affected as well. A knowledge gap was identified within the Adult-Gerontology Acute Care Nurse Practitioner (AG-ACNP) curriculum regarding ethics in crisis standards of care (CSC) medical decision-making. Incorporating a CSC simulation looked to address this knowledge gap. A simulation-based learning (SBL) experience was designed as a critical access setting where CSC are in place and three diverse, medically complex patients in need of critical care present to the hospital where one critical care bed remains open. Given the complexity of the simulation scenario, a table-top pilot test was selected. Three AG-ACNP fourth-quarter students in their critical care rotation volunteered for the pilot test. Students were provided with the topic, “ethics crisis standards of care” and the article, “A catalogue of tools and variables from crisis and routine care to support decision-making during pandemics” by M. Cardona et al. (2021), to read in advance. Students were provided with the triage AI algorithm (M. Cardona et al., 2021) utilizing prognostication tools to prioritize which patient requires the critical care bed. The expectation was that implicit bias would enter the decision-making process, causing deviation from the triage AI algorithm and moral distress. The debriefing session revealed that students deviated from the triage AI algorithm, experienced implicit bias, moral distress, and utilized clinical judgment and experience to care for all three patients. The pilot test results support that a CSC SBL experience addresses a critical knowledge gap in AG-ACNP education and an SBL experience incorporating ethical decision-making curriculum with standardized patients should be developed and trialed as the next step.
Occupational Stress of Pediatric Emergency Nurses in Greece During the COVID-19 Pandemic
Authors: Kasidouli Areti , Matziou Vasiliki , Zyga Sofia , Kasimis Ioannis , Boutopoulou Varvara , Vlachioti Efrosini , Deli Charalampia , Perdikaris Pantelis
Published: January 2024

During the COVID-19 pandemic, numerous studies have shown the high prevalence of occupational stress (OS) of health workers, affecting the quality of health care provided. To date, there is no study regarding OS of emergency care pediatric nurses working in Greece. This study aimed to examine the pediatric nurses' OS working in tertiary public hospitals in Greece. In this cross-sectional study, a total of 104 pediatric nurses were recruited randomly from summer 2020 to summer 2021. The Expanded Nursing Stress Scale (ENSS), which consists of 59 items grouped into nine categories, was used to assess nurses OS. The overall OS mean score was 141.04 (SD = 33.48), indicating mild stress. Among nine categories, pediatric nurses were more stressed about patients and families (mean = 22.83, SD = 5.71), as well as death and dying (mean = 19.33, SD = 5.22), whereas they were less stressed about discrimination (mean = 4.21, SD = 4.09) and problems with peer support (mean = 12.11, SD = 4.58). Sex, age, and shifts did not correlate with OS. Borderline correlation was present between age and inadequate emotional preparation for less experienced nurses (p = 0.047), while higher educated pediatric nurses were more stressed because of workload than lower educated pediatric nurses (p = 0.044). Greek pediatric nurses suffered mild OS during the COVID-19 pandemic. There is a great need for further research and implementation of supportive sustainable programs aimed to the minimization of OS and the optimization of health care provided during and after the COVID-19 pandemic.
Refractory Anti–N-Methyl-d-Aspartate Receptor Autoimmune Encephalitis Induced by Ovarian Teratoma: A Case Report
Authors: Zhang Rui , Zhao Xuemei , Li Wenjing , Gao Yu
Published: January 2024

Objective

Teratoma is a type of germ cell tumor that derived from early embryonic stem cells and germ cell lines, which can lead to a rare complication known as paraneoplastic encephalitis syndrome. Delayed removal of teratoma allows for continuing antigen presentation, inducing affinity maturation of the antibody and the generation of long-lived plasma cells that infiltrate both bone marrow and brain, which makes the patient nonresponsive to later removal of teratoma and refractory to immunotherapy. We present this rare case to remind clinicians to be vigilant for the recognition and removal of teratoma during the treatment of autoimmune encephalitis.

Methods

We retrospectively reviewed the clinical record of this 12-year 5-month-old female patient diagnosed with anti–N-methyl-d-aspartate receptor (anti-NMDAR) autoimmune encephalitis; her ovarian teratoma was unidentified on admission. She did not respond to immunosuppressive therapy until the mature ovarian teratoma identified 45 days after admission and removed the following day, nearly 2 months after symptom onset. This patient experienced nearly complete resolution of symptoms within the subsequent 2 weeks. In addition, we conducted a literature review of the clinical presentations and treatment of anti-NMDAR autoimmune encephalitis associated with ovarian teratoma in the pediatric population.

Results

Our findings suggest that clinicians should be vigilant for the recognition and removal of teratoma during the treatment of autoimmune encephalitis.

Conclusion

Female pediatric patients with suspected anti-NMDAR encephalitis should be screened for ovarian tumors immediately and treated in a multidisciplinary setting including neurology and obstetrics and gynecology.
Detection and Characterization of Microorganisms Linked to Unsealed drugs Sold in Ihiagwa Community, Owerri, Imo State
Authors: Ekeleme Uzochukwu Godswill , Ikwuagwu Vivian O. , Chukwuocha Uchechukwu , Nwakanma Jane , Adiruo Stephanie , Ogini Ikenna , Uche Ude Ifeoma
Published: January 2024

The contamination of pharmaceutical products by microorganisms poses a significant risk to public health. This study was conducted to detect and characterise microorganisms associated with unsealed drugs sold in Ihiagwa community in Owerri, Imo State. A variety of microbiological techniques were employed to analyze samples from unsealed drug containers. The identification process involved morphological, biochemical, and sugar utilisation methods, aiding in the accurate determination of microbial species. Microbial contamination was observed in 42 (84%) out of 50 samples, contaminants included bacteria and fungi. The range of contamination is between 1.2±0.01 × 103 to 2.3±0.02 × 103 cfu/ml for viable count, 0.1±0.02 × 102 to 0.3±0.01 × 102 cfu/g for coliform count and 0.2±0.01 × 101 to 0.5±0.01 × 101 cfu/g for fungi count. The identified microbes were Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. The most common bacterial isolate was Staphylococcus aureus (51.8%), while Candida albicans (73.3%) was the most prevalent fungi. Among the pharmacies and healthcare facilities examined, the Uchems pharmacy had the highest bacterial isolates of 37%, followed by Stepwise pharmacy (22.2%) and the least was Roseline health clinic that recorded 7.4%. The identification of potentially harmful microorganisms in these unsealed drug container samples emphasize the importance of stringent quality control measures, improved handling, storage, and packaging practices to ensure product safety and efficacy especially among drug dealers.
A large-scale cancer-specific protein-DNA interaction network
Authors: Lu Yunwei , Berenson Anna , Lane Ryan , Guelin Isabelle , Li Zhaorong , Chen Yilin , Shah Sakshi , Yin Meimei , Soto-Ugaldi Luis Fernando , Fiszbein Ana , Fuxman Bass Juan Ignacio
Published: January 2024

Cancer development and progression are generally associated with dysregulation of gene expression, often resulting from changes in transcription factor (TF) sequence or expression. Identifying key TFs involved in cancer gene regulation provides a framework for potential new therapeutics. This study presents a large-scale cancer gene TF-DNA interaction network as well as an extensive promoter clone resource for future studies. Most highly connected TFs do not show a preference for binding to promoters of genes associated with either good or poor cancer prognosis, suggesting that emerging strategies aimed at shifting gene expression balance between these two prognostic groups may be inherently complex. However, we identified potential for oncogene targeted therapeutics, with half of the tested oncogenes being potentially repressed by influencing specific activator or bifunctional TFs. Finally, we investigate the role of intrinsically disordered regions within the key cancer-related TF estrogen receptor ɑ (ESR1) on DNA binding and transcriptional activity, and found that these regions can have complex trade-offs in TF function. Altogether, our study not only broadens our knowledge of TFs involved in the cancer gene regulatory network but also provides a valuable resource for future studies, laying a foundation for potential therapeutic strategies targeting TFs in cancer.
Optimal Phylogenetic Reconstruction of Insertion and Deletion Events
Authors: Tule Sanjana , Foley Gabriel , Zhao Chongting , Forbes Michael , Bodén Mikael
Published: January 2024

Insertions and deletions (indels) influence the genetic code in fundamentally distinct ways from substitutions, significantly impacting gene product structure and function. Despite their influence, the evolutionary history of indels is often neglected in phylogenetic tree inference and ancestral sequence reconstruction, hindering efforts to comprehend biological diversity determinants and engineer variants for medical and industrial applications.

We frame determining the optimal history of indel events as a single Mixed-Integer Programming (MIP) problem, across all nodes in a phylogenetic tree adhering to topological constraints, and all sites implied by a given set of aligned, extant sequences. By disentangling the impact on ancestral sequences at each branch point, this approach identifies the minimal indel events that jointly explain the diversity in sequences mapped to the tips of that tree. MIP can recover alternate optimal indel histories, if available.

We evaluated MIP for indel inference on a dataset comprising 15 real phylogenetic trees associated with protein families ranging from 165 to 2000 extant sequences, and on 60 synthetic trees at comparable scales of data and reflecting realistic rates of mutation. Across relevant metrics, MIP outperformed alternative parsimony-based approaches and reported the fewest indel events, on par or below their occurrence in synthetic datasets. MIP offers a rational justification for indel patterns in extant sequences; importantly, it uniquely identifies global optima on complex protein data sets without making unrealistic assumptions of independence or evolutionary underpinnings, promising a deeper understanding of molecular evolution and aiding novel protein design.
Optimizing Accuracy and Efficiency in Analyzing Non-UMI Liquid Biopsy Datasets Using the Sentieon ctDNA Pipeline
Authors: Niu Li , Hu Jinnan , Chen Chuan , Jiang Cai , Chen Haodong , Tang Gongcheng , Liu Ying , Liu Yi
Published: January 2024

Sequencing clinical liquid biopsy, especially circulating tumor DNA (ctDNA), provides a valuable method for identifying low allele frequency tumor variants, opening novel clinical applications, particularly in treatment selection for late-stage cancer patients. Despite advancements, challenges in assay development persist, primarily due to limited sample volumes and insufficiency of reads supporting low allele frequency variants. The allele frequencies of clinically significant variants often hover close to the threshold of errors introduced by PCR and sequencing processes. Therefore, more sophisticated analysis methods are crucial to further reduce base error rates, enabling accurate discrimination between background errors and genuine somatic variants. While several ctDNA analysis pipelines have been published and adopted, there is room for improvement in terms of accuracy and run efficiency.

In this study, we introduce Sentieon’s innovative consensus-based ctDNA pipeline - a rapid and precise solution for calling small somatic variants from non-UMI ctDNA sequencing data. The pipeline comprises four core modules: alignment, consensus generation, variant calling, and variant filtering. Through benchmarking with in-vitro and real clinical datasets, we observed that the Sentieon ctDNA pipeline exhibits higher accuracy compared to alternative methods.
Tracing 600 years of long-distance Atlantic cod trade in medieval and post-medieval Oslo using stable isotopes and ancient DNA
Authors: Martínez-García Lourdes , Pulido Angélica , Ferrari Giada , Hufthammer Anne Karin , Vedeler Marianne , Hirons Alex , Kneale Catherine , Barrett James H. , Star Bastiaan
Published: January 2024

Marine resources have been important for the survival and economic development of coastal human communities across northern Europe for centuries. Knowledge of the origin of such historic resources can provide key insights into fishing practices and the spatial extent of trade networks. Here, we combine ancient DNA and stable isotopes (δ13C, δ15N, non-exchangeable δ2H and δ34S) to investigate the geographical origin of archaeological cod remains in Oslo from the eleventh to seventeenth centuries CE. Our findings provide genetic evidence that Atlantic cod was obtained from different sources, including a variety of distant-water populations like northern Norway and possibly Iceland. Evidence for such long-distance cod trade is already observed from the eleventh century, contrasting with archaeological and historical evidence from Britain and other areas of Continental Europe around the North and Baltic Seas, where such trade developed in a later period. Diverse biological origins are further supported by significant differences of a range of isotopes, indicating that multiple populations living in different environments were exploited. This research highlights the utility of combining ancient DNA methods and stable isotope analysis to describe the development of marine fisheries during the medieval and post-medieval period.
A Biophysical Model for ATAC-seq Data Analysis
Authors: Felce Catherine , Gorin Gennady , Pachter Lior
Published: January 2024

The Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) can be used to identify open chromatin regions, providing complementary information to RNA-seq which measures gene expression by sequencing. Single-cell “multiome” methods offer the possibility of measuring both modalities simultaneously in cells, raising the question of how to analyze them jointly, and also the extent to which the information they provide is better than unregistered data where single-cell ATAC-seq and single-cell RNA-seq are performed on the same sample, but on different cells. We propose and motivate a biophysical model for chromatin dynamics and subsequent transcription that can be used with multiome data, and use it to assess the benefits of multiome data over unregistered single-cell RNA-seq and single-cell ATAC-seq. We also show that our model provides a biophysically grounded approach to integration of open chromatin data with other modalities.
Application of hybrid failure mode effect analysis based on fuzzy AHP and fuzzy TOPSIS in quality risk assessment of fixed-dose artemether-lumefantrine tablets
Authors: Ilyasu Salim , Malami Sani , Khalid Garba Mohammed , Abdussalam Umar Sharif , Dawud Abubakar Magaji , Mohammed Saratu , Falalu Al-Kasim Rabiu , Zaharadeen Mustapha Fatima , Sani Farouq Idris , Manu Abdussalam Yayo , Yakasai Ibrahim Adamu , Chedi Basheer Abba-Zubair , Bello Aminu Sahalu , Ibrahim Adam Bashir , Julde Saadatu , Idris Maryam Shehu , Bichi Lawal Alhassan
Published: January 2024

Background

A hybrid Failure Mode Effect Analysis (FMEA) based on fuzzy logic and multicriteria decision analytics was applied as a post-marketing surveillance tool for troubleshooting potential quality problems of Artemisinin Combination Therapies (ACTs) as a means of aggregating subjective opinions of quality experts in providing vital information for continuous management and improvement of safety and quality standards.

Research design and methods

An FMEA team of five cross-functional quality experts implemented a hybrid fuzzy FMEA model based on Analytical Hierarchy Process (AHP) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) to solve multicriteria decision problems in quality risk analysis of historic quality control data of ACTs.

Results

Expert opinions were captured as triangular fuzzy numbers to represent the linguistic scoring of risk-determining variables for fifteen failure modes. The fuzzy AHP enabled systematic ranking of the variables, while the fuzzy TOPSIS algorithm provided easily understood and configurable computational procedures for ranking the failure modes based on optimal geometric paths to positive and negative ideal solutions.

Conclusions

The quality risk of ACTs could be reliably established using the fuzzy FMEA where aggregated experts’ decisions and risk variables’ weights are of considerable importance to the final ranking of quality failures.
Understanding community leaders’ and program coordinators’ perceptions of and needs from a community systems map: a qualitative study
Authors: Lo Margret , Ross Natasha , Anand Sonia S. , de Souza Russell J , Wahi Gita , Desai Dipika , Kandasamy Sujane , Sherifali Diana , DiLiberto Deborah , Newbold K. Bruce , Crea-Arsenio Mary , Montague Patty , Jackson-Best Fatimah
Published: January 2024

Objectives

A systems map for the Riverdale community in Hamilton, Ontario has documented programs, activities, and spaces for healthy, nature-based activities. A systems map was created to provide an approachable resource for community members. As a means of understanding whether this map would prove useful, interviews with community and organization leaders were conducted. The objectives of this study were to 1) characterize user engagement with recreational and active living programs and services located in and around the Riverdale community, 2) determine existing barriers to and facilitators of accessing recreational and active living programs for those in the Riverdale community, as perceived by those who deliver programs and, 3) improve the functionality and usability of the system map, including any information or services that may be missing.□□

Methods

Twenty 60-minute semi-structured interviews were conducted with community leaders and program coordinators who focus on healthy active living and work within the Riverdale community.

Results

We learned that Riverdale programming is typically gender-specific, women-dominated, and targeted to children and youth. Additionally, cost, transportation and accessibility, and language were the greatest barriers to accessing recreational programming. Conversely, facilitators for program involvement included transportation assistance, compensation, and food provision. Finally, interviews revealed the need for sustainability, clarity, and language options within the systems map.

Conclusion

This work procured the necessary information to edit the interactive systems map according to community needs. With this map, Riverdale community members are able to access a source of information about activities and services.
Quality of maternal care at public health centers of Siltie zone, Central Ethiopia 2022
Authors: Mohammednur Abdulfeta Shafi , Abdu Neima Ridwan
Published: January 2024

Introduction

Quality of care is “the extent to which health care services provided to individuals and patient populations improve desired health outcomes. In order to achieve this, health care must be safe, effective, timely, efficient, equitable and people-centered (WHO). Quality care is crucial in ensuring that women and newborns receive interventions that may prevent and treat birth-related complications. This paper assessed the quality of maternal care at public health facilities of Siltie zone, Central Ethiopia, from March 1 up to April, 15, 2023.

Method

facility based Cross sectional study design was conducted. Under this study totally 437 individuals’, 367 mothers and 70 health care providers in 23 health center were interviewed. All woreda and city administrates were included in the study contributing at least one health center. The data collection tool was adopted from health sector transformation in quality in Ethiopia (HSTQ). Specific health center maternal health care quality score was obtained by the total score of the health center performed divided by the total score expected (excluding NA quality measures) and the result was multiplied by 100%.

Result

Overall quality of sanitation facility in health center is 71% and the overall quality of care service based on the health care provider is almost 80.7%. Quality of prenatal health care service is 83%, Labor and Newborn care is 87%, postpartum care 87%and Facility inventory 77%. The overall quality of maternal care is 82%.

Conclusion

Quality of maternal and newborn health care service is good. Further efforts are needed to improve availability of necessary equipment’s, electricity and water supply.
Validation of the Food Safe Zone Questionnaire for Families of Individuals with Prader-Willi syndrome
Authors: Dykens Elisabeth M , Roof Elizabeth , Hunt-Hawkins Hailee
Published: January 2024

Prader-Willi syndrome (PWS), a genetic neurodevelopmental disorder, is characterized by hyperphagia and significant behavioral problems. Hyperphagic individuals with PWS are chronically hungry yet rarely feel sated, and often engage in food-seeking behaviors. To avoid obesity in their children, families implement food security and supervision strategies (e.g., locking food sources, alerting others). Yet such accommodations may undermine parental appraisals of hyperphgia (e.g., it’s not a problem as we lock food); a potential confound in clinical trials aimed at attenuating hyperphagia. We developed the Food Safe Zone (FSZ) questionnaire to remind parents of their food safety practices prior to them evaluating their child’s hyperphagia.

Our team developed 20 FSZ items that were revised for clarity and completeness in an iterative feedback process with stakeholders; parents, PWS specialists, and individuals with PWS. The FSZ was pilot tested, descriptive findings were reviewed by additional stakeholders, and then administered to 624 parents in a large-scale study. Based on an open-ended question, “Is there anything else you do to ensure food safety?” two additional items were added and evaluated in a follow-up study.

Principal component analyses revealed that 21 FSZ items loaded onto 5 factors that were readily interpretable, accounting for 67% of test variance: Alerting Others and Food Supervision in the Community; Locking or Restricting Food Sources; Checking for Food; At Home Supervision and Meals; and Avoiding Food Settings. Internal consistency and test-rest reliability were robust. Convergent validity analyses revealed that regardless of age, parents implemented more FSZ strategies in response to the severity of their child’s hyperphagia.

The psychometrically sound FSZ stands to enhance accurate parental assessments of hyperphagia in future studies or clinical trials. Analyses of the open-ended question also shine a light on the extraordinary measures that parents use to ensure the health of their individual with PWS.
Physical activity and prevalence of constipation in Japanese young people
Authors: Watanabe Junichi , Furukawa Shinya , Yamamoto Yasunori , Kato Aki , Kusumoto Katsunori , Takeshita Eiji , Ikeda Yoshio , Yamamoto Naofumi , Saeki Yuka , Miyake Teruki , Yoshida Osamu , Hiasa Yoichi
Published: January 2024

Background

Constipation is a very common medical issue among general humans worldwide. The association between physical activity (PA) and constipation is still inconsistent. Additionally, no evidence regarding this issue in young population.

Aims

This study aimed to evaluate the association between self-reported physical activity and constipation in Japanese young population, taking the presence or absence of an exercise partner as an additional variable.

Methods

The study subjects consisted of 12497 Japanese university students. Information on constipation, exercise frequency, exercise intensity, and exercise partners was obtained from a self-administered questionnaire. Age, sex, body mass index, drinking, smoking, anemia, and sports injury were selected as potential confounding factors.

Results

The prevalence of constipation was 6.5% in this cohort. Low, moderate, and high frequency of exercise was independently inversely associated with constipation (adjusted odds ratios [a OR] were low: a OR 0.77 [95% confidence interval (CI) 0.63–0.94], moderate: a OR 0.75 [95% CI 0.60–0.94] and high: a OR 0.70 [95% CI 0.53–0.91], p for trend p=0.002). Low, moderate, and high intensity of exercise was independently inversely associated with constipation (low: a OR 0.77 [95% CI 0.62–0.97], moderate: a OR 0.77 [95% CI 0.63–0.95] and high: a OR 0.70 [95% CI 0.53–0.87], p for trend p=0.001). Exercise with groups and with friends was independently inversely associated with constipation whereas the association between exercising alone and constipation was not significant (groups: a OR 0.70 [95% CI 0.53–0.90] and friends: a OR 0.56 [95% CI 0.42–0.74])

Conclusion

In the young Japanese population, frequency and intensity of exercise and presence of exercise partner might be independently inversely associated with constipation.
Wearable Sensor and Digital Twin Technology for the Development of a Personalized Digital Biomarker of Vaccine-Induced Inflammation
Authors: Steinhubl Steven R. , Sekaric Jadranka , Gendy Maged , Guo Huaijian , Ward Matthew P. , Goergen Craig J. , Anderson Jennifer L. , Amin Sarwat , Wilson Damen , Paramithiotis Eustache , Wegerich Stephan
Published: January 2024

Effective response to vaccination requires activation of the innate immune system, triggering the synthesis of inflammatory cytokines. The subjective symptoms related to this, referred to as reactogenicity, affect a variable percentage of vaccinated people to different degrees, with evidence supporting a relationship between the severity of symptoms a person experiences and their eventual immune response. Wearable sensors allow for the identification of objective evidence of physiologic changes a person experiences in response to vaccine-induced inflammation, but as these changes are subtle, they can only be detected when an individual’s pre-vaccination normal variability is considered. We used a wearable torso sensor patch and a machine learning method of similarity-based modeling (SBM), which learns the dynamic interplay between multivariate input sources, to create a physiologic digital twin for 88 people receiving 104 vaccine doses. By effectively removing expected variations and leaving only vaccine-induced differences, we developed a multivariate digital biomarker that incorporates changes in multiple continuously monitored physiologic data streams to measure the degree and duration of vaccine induced inflammation. This objective measure correlated with subjective symptoms, and in a 20-person subset, both humoral and cellular immunogenicity.
Modeling lesion transition dynamics to clinically characterize mpox patients in the Democratic Republic of the Congo
Authors: Nishiyama Takara , Miura Fuminari , Jeong Yong Dam , Nakamura Naotoshi , Park Hyeongki , Ishikane Masahiro , Yamamoto Shotaro , Iwamoto Noriko , Suzuki Michiyo , Sakurai Ayana , Aihara Kazuyuki , Watashi Koichi , Hart William S , Thompson Robin N , Yasutomi Yasuhiro , Ohmagari Norio , Kingebeni Placide Mbala , Huggins John W. , Iwami Shingo , Pittman Phillip R.
Published: January 2024

Coinciding with the global outbreak of clade IIb mpox virus (MPXV), the Democratic Republic of the Congo (DRC) recently experienced a rapid surge in mpox cases with clade I MPXV. Clade I MPXV is known to be more fatal, but its clinical characteristics and prognosis differ between patients. Here, we used mathematical modelling to quantify disease progression in a large cohort of mpox patients in the DRC from 2007-2011, particularly focusing on lesion transition dynamics. We further analyzed individuals’ clinical data to find predictive biomarkers of severity of symptoms. Our analysis shows that mpox patients can be stratified into three groups according to symptom severity, and that viral load at symptom onset may serve as a predictor to distinguish groups with the most severe or mild symptoms after progression. Understanding the severity and duration of symptoms in different patients, as characterized by our approach, allows treatment strategies to be improved and individual-specific control measures (e.g isolation strategies based on disease progression) to be developed.