bluuebunny/crossref_metadata_2025 huggingface dataset:
Protandric simultaneous hermaphroditism inSalmoneus carvachoiAnker, 2007 (Decapoda: Alpheidae): a new sexual system in alpheid shrimps
Authors: Oliveira Mário Vitor , Baeza Juan Antonio , Guéron Rodrigo , Costa-Souza Ana Carla , Mariano Rodolfo , Zara Fernando José , Almeida Alexandre O
Published: October 2023

In caridean shrimps, sexual systems vary from gonochorism to various forms of hermaphroditism. The shrimp Salmoneus carvachoi has been reported to exhibit both male (appendix masculina) and female (brooding embryos) anatomical characteristics simultaneously. Our aim was to examine the sexual system of S. carvachoi and to test the hypothesis of protandric simultaneous hermaphroditism (PSH) in this species. We analysed internal and external features using microscopy and histology techniques. Our analyses support the hypothesis of PSH in S. carvachoi and enabled the identification of male-phase and hermaphroditic individuals. All individuals exhibit a well-developed appendix masculina on the endopods of the second pleopods; however, small male-phase individuals possess only male gonopores, whereas larger hermaphroditic individuals possess both female and male gonopores. Hermaphrodites exhibit both male and female germinative cells in various stages of development, as well as an androgenic gland. Our study describes a novel sexual system for alpheids and provides a detailed description of anatomical traits in S. carvachoi. Studies that describe sexual systems in Alpheidae may shed light on the evolutionary history of gender expression in carideans and how environmental conditions favour sex allocation in decapods and other invertebrates.
Adherent Abdominal Scar Revision Does Not Require Total Scar Removal
Authors: Lumintang Loelita Marcelia , Dohi Teruyuki , Ogawa Rei
Published: October 2023

Abdominal surgery can cause notable scars that adhere to the abdominal tissues below. Full scar removal is generally not recommended due to the risk of intestinal damage and delayed wound healing. Here, we describe a surgical scar-revision procedure for adherent abdominal scars that does not involve either opening the abdominal cavity or total scar removal. A 58-year-old woman exhibited an aesthetically displeasing hypertrophic adherent abdominal scar that extended from the umbilical fold to the pubic area and distorted the umbilicus. It arose from multiple laparotomies for hernia repair and subsequent complications. Pain/discomfort and functional impairment were absent. Scar-revision surgery was conducted under general anesthesia. The skin around the adherent scar was excised down to the subcutaneous layer with a minimal margin. However, only the epidermis and superficial dermal layer of the adherent scar were removed; the deep scar dermis remained. The skin flaps on either side of the midline were then advanced and sutured over the remnant dermis. One year after surgery, the aesthetic and functional outcomes were excellent. Furthermore, no hypertrophic scars or epidermal cysts were found. This technique is effective, efficient, does not involve intraabdominal procedures, provides a vascularized tissue layer, and results in an aesthetically pleasing scar.
Inflammatory mechanisms in post-traumatic osteoarthritis: a role for CaMKK2
Authors: Riggs Keegan C. , Sankar Uma
Published: October 2023

Post-traumatic osteoarthritis (PTOA) is a multifactorial disease of the cartilage, synovium, and subchondral bone resulting from direct joint trauma and altered joint mechanics after traumatic injury. There are no current disease-modifying therapies for PTOA, and early surgical interventions focused on stabilizing the joint do not halt disease progression. Chronic pain and functional disability negatively affect the quality of life and take an economic toll on affected patients. While multiple mechanisms are at play in disease progression, joint inflammation is a key contributor. Impact-induced mitochondrial dysfunction and cell death or altered joint mechanics after trauma culminate in inflammatory cytokine release from synoviocytes and chondrocytes, cartilage catabolism, suppression of cartilage anabolism, synovitis, and subchondral bone disease, highlighting the complexity of the disease. Current understanding of the cellular and molecular mechanisms underlying the disease pathology has allowed for the investigation of a variety of therapeutic strategies that target unique apoptotic and/or inflammatory processes in the joint. This review provides a concise overview of the inflammatory and apoptotic mechanisms underlying PTOA pathogenesis and identifies potential therapeutic targets to mitigate disease progression. We highlight Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a serine/threonine protein kinase that was recently identified to play a role in murine and human osteoarthritis pathogenesis by coordinating chondrocyte inflammatory responses and apoptosis. Given its additional effects in regulating macrophage inflammatory signaling and bone remodeling, CaMKK2 emerges as a promising disease-modifying therapeutic target against PTOA.
COVID-19 Infection and Diabetes
Authors: Gomaa Ahmed Fathy , Elghmary Reda M. , Sharafeddin Mahmoud A. , Mohamed Salem Youssef , Elsayed Ayman Fathy
Published: October 2023

Background

Hyperglycemia is one of the most important independent risk factors that affect the prognosis and outcome of COVID-19 patients. Coronavirus disease 2019 infection is associated with poor glycemic control. This study's objectives were to determine the effect of hyperglycemia on the prognosis and outcome of COVID-19 patients and to detect whether COVID-19 infection can induce new-onset diabetes.

Patients and Methods

This cohort study was carried out on 240 hospitalized Egyptian COVID-19 patients, at Zagazig University Hospital isolation intensive care unit, between March 2020 and March 2021. They compared patients with diabetes and uncontrolled hyperglycemia against each other and COVID-19 patients without diabetes or uncontrolled hyperglycemia. Baseline demographic data, clinical features, and laboratory analysis were collected. Clinical outcome was evaluated via hospital stay and survival rate. Patients with uncontrolled hyperglycemia and nondiabetic patients were followed up 1 year after the hospital discharge to detect the development of new-onset diabetes.

Result

The diabetic group had the highest creatinine level, and the nondiabetic group had a minor C-reactive protein and D-dimer. The difference is significant between diabetic and nondiabetic groups concerning hospital stay. The nondiabetic group had the shortest hospital stay. There is a statistically substantial relationship between mortality and the glycosylated hemoglobin, serum creatinine, C-reactive protein, D-dimer, and serum ferritin. A total of 46.6% of survivors in the uncontrolled hyperglycemic group and 3.4% in the nondiabetic group developed diabetes mellitus during follow-up. There is a statistically significant relationship between new-onset diabetes mellitus and D-dimer.

Conclusions

Coronavirus disease 2019 can induce diabetes mellitus in vulnerable patients (presented with uncontrolled hyperglycemia at admission). In addition, COVID-19 patients with diabetes or uncontrolled hyperglycemia have worse outcomes and poor prognoses.
Microsporidial Stromal Keratitis, a Case Report
Authors: Duangpraphat Monchai , Changpradub Dhitiwat , Chueansuwan Worawong
Published: October 2023

Ophthalmic manifestation in Microsporidium spp. was observed in this patient having experienced decreased vision at the right eye for 1 month. The patient worked as an organic farmer. She was at risk because of exposure to water while watering plants. The confocal microscopy performed on the right eye showed marked dendritic cells. The corneal biopsy was proven by tiny dot-like organisms in acid-fast stain and modified acid-fast stain. In addition, the positive polymerase chain reaction test result for Microsporidium spp. supported the diagnosis. The patient was treated with an intensive course of topical biguanides, antimicrobial agents, and penetrating keratoplasty.
Correlation Between Quality of Life and Speech Recognition Outcomes Following Cochlear Implantation
Authors: Dorismond Christina , Patro Ankita , Holder Jourdan T. , Perkins Elizabeth L.
Published: October 2023

Objective

To study the relationship between Cochlear Implant Quality of Life-10 Global (CIQOL-10) scores and speech recognition scores 6 and 12 months after cochlear implantation (CI) and to compare CIQOL-10 scores for patients who met the benchmark speech recognition scores with those who did not.

Study Design

Retrospective review.

Setting

Tertiary referral center.

Patients

One hundred twenty-four adults who underwent CI between 2018 and 2021 and completed a CIQOL-10 questionnaire at their 6- and/or 12-month postoperative visit.

Main Outcome Measure(s)

CIQOL-10, Consonant-Nucleus-Consonant (CNC) word, and AzBio in quiet and noise scores.

Results

At 6 months, weak positive correlations were found between CIQOL-10 and CNC (n = 78,r= 0.234,p= 0.039) and AzBio in quiet (n = 73,r= 0.293,p= 0.012) scores but not AzBio in noise scores (n = 39,r= 0.207,p= 0.206). At 12 months, weak positive correlations were found between CIQOL-10 and CNC (n = 98,r= 0.315,p= 0.002), AzBio in quiet (n = 88,r= 0.271,p= 0.011), and AzBio in noise (n = 48,r= 0.291,p= 0.045) scores. Patients who met the benchmark CNC scores had notably higher CIQOL-10 scores than those who did not at 6 months (52.0 vs 45.5,p= 0.008) and 12 months (52.0 vs 45.5,p= 0.003). A similar relationship was found for those who met the benchmark AzBio in quiet scores at both 6 months (52.0 vs 44.0,p= 0.006) and 12 months (52.0 vs 46.5,p= 0.011).

Conclusion

CIQOL-10 scores have weak positive correlations with postoperative speech recognition outcomes at 6 and 12 months. This highlights the need for the continued use of quality-of-life measures, such as the CIQOL-10, in assessing CI outcomes to gain a more comprehensive understanding of patients' experiences.
Electrocautery ablation of high-grade anal intraepithelial lesions: A protocol for a clinical trial
Authors: Ando Naokatsu , Mizushima Daisuke , Kitamura Hiroshi , Shiojiri Daisuke , Nakamoto Takato , Takano Misao , Aoki Takahiro , Oka Shinichi , Gatanaga Hiroyuki
Published: October 2023

Background:

Anal cancer is predominantly caused by the human papillomavirus. The use of high-resolution anoscopy (HRA) for screening, followed by appropriate therapeutic interventions, is progressively being acknowledged as a standardized procedure to manage anal cancer. Commonly, lesions identified as potentially high-grade squamous intraepithelial lesions undergo biopsy and receive treatment if classified as anal intraepithelial neoplasia (AIN) grade 2 or 3. Numerous studies have underscored the substantial efficacy of electrocautery ablation in treating grade 2 or 3 AIN. However, relapse within and outside the targeted areas after intervention is a clinical problem. Postintervention recurrence within and beyond the initial targeted areas presents a significant clinical challenge. Most healthcare facilities in Japan do not offer electrocautery ablation. An initial pilot study demonstrated the safety and efficacy of electrocautery ablation. Consequently, we aimed to scrutinize the effectiveness and safety profile of electrocautery ablation procedures using a larger sample size.

Methods:

This single-arm, open-label intervention trial aims to examine the efficacy and safety associated with electrocautery ablative treatments by utilizing high-frequency medical instruments. The cohort will comprise patients diagnosed with grade 2 or 3 AIN who will then undergo ablative treatments. Subsequent follow-ups will be scheduled at intervals of 6, 12, 24, and 36 months posttreatment, incorporating HRA-guided sextant biopsies to monitor disease progression. To minimize the chances of overlooking the lesions before and after the treatment phase, systematic HRA-guided sextant biopsies will be performed. Within the scope of this study, a sextant biopsy necessitates a minimum of 6 biopsy procedures in various directions, irrespective of any abnormalities detected during HRA inspections. The principal objective of this study is to ascertain the 12-month recurrence rate, with secondary objectives focusing on monitoring adverse events and recurrence rates at the 6-, 24-, and 36-month time points.

Conclusion:

This study aims to provide substantial data concerning the effectiveness and safety parameters of electrocautery ablation as a viable alternative treatment for patients with grade 2 or 3 AIN.
Concordance of National Insurance Criteria with WPATH Standards of Care for Gender-Affirming Surgery
Authors: Diaddigo Sarah E. , LaValley Myles N. , Asadourian Paul A. , Feuer Grant B. , Warner Paige E. , Rohde Christine H.
Published: October 2023

Background:

Given that gender-affirming surgery (GAS) is considered medically necessary for transgender and gender-diverse individuals who desire it, the aim of this study was to assess the concordance of insurance criteria for GAS with the most recent World Professional Association for Transgender Health Standards of Care for the Health of Transgender and Gender Diverse People, Version 8.

Methods:

Insurance policies for coverage of gender-affirming genital surgery (“bottom surgery”), chest surgery (“top surgery”), and facial reconstruction from companies representing 80% of the market coverage in each state were evaluated. Policies were classified into 3 categories: no coverage, case by case, or preauthorization. Among preauthorization policies, criteria for coverage of specific procedures were analyzed for adherence to the Standards of Care for the Health of Transgender and Gender Diverse People, Version 8.

Results:

Bottom-surgery policies were most concordant for age and gender dysphoria criteria, and transmasculine top surgery policies were most concordant for hormone therapy, continuous living in a congruent gender role, and referral criteria. Transfeminine top surgery criteria were more restrictive than transmasculine criteria. The most discordant criteria were for hormone therapy, being required for at least 12 months before surgery in the majority of surveyed policies. Many specific procedures and treatments were excluded, especially facial GAS with cosmetic overlap. Reversal and revisionary procedures were covered by less than 25% of policies.

Conclusions:

Compared with previous literature, insurance coverage and criteria alignment are becoming more concordant with medical guidelines. However, significant barriers to care for GAS remain.
A Comparison of Endoscope-Assisted and Open Frontoorbital Distraction for the Treatment of Unicoronal Craniosynostosis
Authors: Wagner Connor S. , Pontell Matthew E. , Barrero Carlos E. , Salinero Lauren K. , Heuer Gregory G. , Swanson Jordan W. , Taylor Jesse A.
Published: October 2023

Background:

Frontoorbital distraction osteogenesis (FODO) is an established surgical technique for patients with unicoronal craniosynostosis. The authors’ institution has used an endoscope-assisted technique (endo-FODO) in recent years to decrease cutaneous scarring and lessen the impact on the functional growth matrix. This study compared perioperative outcomes in patients undergoing endo-FODO to those in patients undergoing the traditional coronal approach.

Methods:

Patients with unicoronal craniosynostosis undergoing FODO from 2013 to 2023 were included, and grouped by whether they underwent endo-FODO or a traditional coronal incision. Operative time, estimated blood loss, transfusion volume, and length of hospitalization were compared. Cutaneous scarring at 1 year postoperatively was assessed with the Scar Cosmesis Assessment and Rating (SCAR) scale.

Results:

A total of 27 patients (18 traditional and 9 endoscope-assisted) with an average age of 5.6 months (interquartile range [IQR], 5.1 to 6.3 months) at surgery were included, with no difference between groups (P = 0.999). Operative time was 114 minutes (IQR, 92 to 122 minutes) for traditional FODO and 104 minutes (IQR, 95 to 112 minutes) for endo-FODO (P = 0.607). Time under anesthesia was shorter for endo-FODO (traditional, 243 minutes [IQR, 218 to 264 minutes]; endo-FODO, 210 minutes [IQR, 191 to 224 minutes]; P = 0.029). Transfusion volume was 12.2 mL/kg lower for endo-FODO compared with traditional FODO (P = 0.001). Length of stay was similar between groups (P = 0.678). SCAR ratings were 1.83 (IQR, 1.1 to 4.47) in traditional FODO compared with 1.00 (IQR, 0.58 to 1.67) in the endo-FODO (P = 0.036).

Conclusions:

Endo-FODO was associated with reduced time under anesthesia, reduced transfusion requirements, and improved SCAR scores, with no change in duration of surgery, perioperative complications, or length of stay. Future work will compare functional and aesthetic outcomes between techniques.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Does an alternative breast support garment provide symptomatic relief for larger breasted women with chronic non-specific back pain?
Authors: Haworth Lauren , May Karen , Janssen Jessie , Selfe James , Chohan Ambreen
Published: October 2023

Background:

Nonsurgical guidelines recommend implementing a correctly fitted bra when managing back pain among larger breasted women. Achieving this is challenging with current bra solutions, sizing principles, and fitting approaches. Persistent wearing of an ill-fitting bra can cause negative health implications, including non-specific back pain.

Objectives:

This study investigated immediate and short-term biomechanical and pain responses to changing breast support garment among larger breasted women with non-specific back pain.

Methods:

Participants (n = 24) performed a standing task, drop jumps, and seated typing tasks while bra and spinal kinematic data were recorded. Five breast support conditions were assessed: participants’ usual bra (control), a professionally fitted bra in the immediate term (standard) and after 4 weeks wear (standard28), and a bra with an alternative design, measurement, and fitting approach in both the immediate term (alternative) and after 4 weeks wear (alternative28). A bra fit assessment and clinical pain/disability questionnaires were included.

Results:

All participants failed the bra fit assessment in the control bra, compared with 87.5% (n = 21) in the standard and 4.2% (n = 1) in the alternative bras. The standard28 and alternative28 bras provided symptomatic relief, with the alternative28 bra improving a greater number of outcome measures. Reduced nipple-sternal-notch distance was observed only in the alternative28 bra condition.

Conclusions:

Symptomatic relief may be associated with the resting position of the breast tissue on the anterior chest wall. The alternative bra may provide potential clinical benefit if implemented as part of a nonsurgical or conservative pain management strategy. Alternative breast support garments should be considered to provide solutions to the problems associated with traditional bras.
68Ga-LNC-1007 PET/CT Imaging in a Patient With Renal Cell Carcinoma Compared With 68Ga-PSMA-11 PET/CT
Authors: Lin Rong , Wang Chao , Xu Fuqi , Zang Jie , Miao Weibing
Published: October 2023

A 57-year-old man was incidentally found with 3 lesions located in bilateral kidneys, which were finally diagnosed as renal cell carcinoma (RCC) by postoperative pathology. 68Ga-LNC-1007, also denoted as 68Ga-FAPI-RGD, was synthesized from fibroblast activation protein inhibitor-02 (FAPI-02) and cyclic arginine-glycine-aspartate (RGD), which could target both FAP and integrin αvβ3. RCC lesions demonstrated only slight 68Ga-PSMA uptake, but intense tracer uptake on 68Ga-LNC-1007 PET/CT. This case demonstrates the potential value of 68Ga-LNC-1007 PET/CT for the evaluation of RCC.
18F-PSMA-1007 PET/CT in a Case of Von Hippel-Lindau Syndrome
Authors: Dong Aisheng , Zhao Bo , Wang Linhui , Cheng Chao , Zuo Changjing
Published: October 2023

We describe 18F-PSMA-1007 PET/CT findings in case of von Hippel-Lindau syndrome with a cerebellar hemangioblastoma, 6 renal cell carcinomas in the bilateral kidneys, cystic lesions in the pancreas and left adrenal gland, and solid lesions in the bilateral epididymides. 18F-PSMA-1007 PET/CT showed intense activity with SUVmax of 111.3 of the cerebellar hemangioblastoma, variable activity with SUVmax range of 6.4–37.6 of the renal cell carcinomas, and increased activity of the bilateral epididymal lesions (SUVmax of 5.1 and 8.2 for the left and right epididymal lesions, respectively).
Coexistence of FDG-Avid and FDG-Negative Aneurysms in a Patient With Fever of Unknown Origin
Authors: Lv Yuhu , Shao Fuqiang , Jia Qing , Lan Xiaoli , Qin Chunxia
Published: October 2023

A 68-year-old man with intermittent fever of unknown origin for 5 months underwent 18F-FDG PET/CT to detect causative lesion. An 18F-FDG–avid lesion was revealed in the left pelvic iliac vessel region and was highly suggestive of malignancy. One and a half months later, a giant left internal iliac artery aneurysm was identified by CT angiography, corresponding to the 18F-FDG–avid lesion. Combined with elevated inflammatory markers, he was finally diagnosed as having inflammatory internal iliac artery aneurysm. An abdominal aortic aneurysm with low 18F-FDG uptake was also identified.
68Ga-DOTATATE PET/CT of Metastatic Lymphoepithelial Carcinoma of Parotid Gland
Authors: Low Han Chung , Loke Kelvin Siu Hoong , Wang Fu Qiang , Han Shuting , Nei Wen Long
Published: October 2023

We present a case of a 59-year-old woman with lymphoepithelial carcinoma of left parotid gland. She was treated with radical radiotherapy, but her plasma Epstein-Barr virus DNA load continued to increase despite good locoregional response. As her primary tumor was positive for somatostatin receptor type 2, we performed 68Ga-DOTATATE PET/CT, which revealed multiple DOTATATE-avid distant metastases.
A Unique Case of Familial Expansile Osteolysis
Authors: Pitot Marika A. , Broski Stephen M. , Baffour Francis , Powell Garret M.
Published: October 2023

Familial expansile osteolysis is an exceedingly rare autosomal dominant bone dysplasia, which can have overlapping features with Paget disease and expansile skeletal hyperphosphatasia. We present a novel case of familial expansile osteolysis evaluated on 99mTc-MDP bone scan with correlative radiographs and CT.
FDG PET/CT Findings of Renal Cell Carcinoma Arising From a Transplanted Kidney in a Pediatric Patient
Authors: Fleury Anilawan S. , Zhuang Hongming
Published: October 2023

A 12-year-old girl presented with a history of kidney transplant complicated by posttransplant lymphoproliferative disease. A solid mass was found in the lower pole of the transplanted kidney, concerning for posttransplant lymphoproliferative disease. However, biopsy confirmed papillary renal cell carcinoma. FDG PET/CT showed increased activity in the known renal cell carcinoma in the renal allograft.
18F-Fluorocholine PET/CT in the Detection of Hyperfunctioning Transplanted Parathyroid Tissue
Authors: Garrou Federico , Rizzo Alessio , Rosso Daniela , Bondi Stefano , Racca Manuela
Published: October 2023

A 54-year-old woman diagnosed with multiple endocrine neoplasia syndrome type 1 and primary hyperparathyroidism underwent total parathyroidectomy with autotransplantation of parathyroid tissue fragments in the right forearm in 1999. Since several years later, follow-up laboratory examinations showed the relapse of hypercalcemia; the patient started cinacalcet therapy. To exclude the presence of hyperfunctioning parathyroid glands in ortotopic or ectopic sites, a PET/CT scan with 18F-fluorocholine was performed. The PET/CT scan excluded the presence of ortotopic and ectopic parathyroid glands but showed a hyperplastic parathyroid fragment in the right forearm, responsible for the patient’s persistent hypercalcemia.
Protein Phosphatase 2A Activation Promotes Heart Transplant Acceptance in Mice
Authors: Zhou Xianming , Xu Qian , Li Wangzi , Dong Nianguo , Stomberski Colin , Narla Goutham , Lin Zhiyong
Published: October 2023

Background.

Although heart transplantation is the definitive treatment for heart failure in eligible patients, both acute and chronic transplant rejection frequently occur. Protein phosphatase 2A (PP2A) activity is critical in maintaining tissue and organ homeostasis. In this study, we evaluated the effect of a novel class of small molecule activators of PP2A (SMAPs) on allograft rejection in a mouse heterotopic heart transplantation model.

Methods.

Recipient mice were administered with DT-061 (a pharmaceutically optimized SMAP) or vehicle by oral gavage beginning 1 d after transplantation. Histological and immunofluorescence analyses were performed to examine allograft rejection. Regulatory T cells (Treg) from recipient spleens were subjected to flow cytometry and RNA sequencing analysis. Finally, the effect of DT-061 on smooth muscle cells (SMCs) migration and proliferation was assessed.

Results.

DT-061 treatment prolonged cardiac allograft survival. SMAPs effectively suppressed the inflammatory immune response while increasing Treg population in the allografts, findings corroborated by functional analysis of RNA sequencing data derived from Treg of treated splenic tissues. Importantly, SMAPs extended immunosuppressive agent cytotoxic T lymphocyte–associated antigen-4-Ig–induced cardiac transplantation tolerance and allograft survival. SMAPs also strongly mitigated cardiac allograft vasculopathy as evidenced by a marked reduction of neointimal hyperplasia and SMC proliferation. Finally, our in vitro studies implicate suppression of MEK/ERK pathways as a unifying mechanism for the effect of PP2A modulation in Treg and SMCs.

Conclusions.

PP2A activation prevents cardiac rejection and prolongs allograft survival in a murine model. Our findings highlight the potential of PP2A activation in improving alloengraftment in heart transplantation.
An Examination of the Relationship Between Exposure to Bisphenol A and Attention-Deficit/Hyperactivity Disorder in Children and Adolescents
Authors: Baykal Saliha , Nalbantoğlu Ayşin
Published: October 2023

Objectives

Exposure to environmental toxic agents in the prenatal and/or postnatal periods may play in the acquired development of attention-deficit/hyperactivity disorder (ADHD) in groups with genetic risks. Bisphenol A (BPA) is a widely used industrial chemical with neurotoxic effects. This study examined the relationship between exposure to BPA and clinical ADHD.

Methods

This cross-sectional, case-controlled clinical study compared 45 drug-naive children and adolescents with ADHD and 30 healthy controls in terms of serum BPA levels. Psychiatric comorbidities in the ADHD group were determined using the “Schedule for Affective Disorders and Schizophrenia for school-aged children, lifetime version.” The Child Behavior Checklist (CBCL) was also administered to all participants.

Results

Serum BPA levels were significantly higher in the ADHD group than in the healthy control group. In addition, significant, weak positive correlation was found between BPA levels and CBCL attention and CBCL total problem scores.

Conclusions

Our results show that BPA may be an environmental toxic agent with a potential role in the etiology of ADHD and particularly attention deficiency. Preventive interventions can be developed if this can be confirmed with longitudinal studies and repeated measurements.
Optimization of high-throughput 16S rRNA gene amplicon sequencing: an assessment of PCR pooling, mastermix use and contamination
Authors: Aggarwal Dinesh , Rajan Diana , Bellis Katherine L. , Betteridge Emma , Brennan Joe , de Sousa Catarina ,   CARRIAGE Study Team‡, Parkhill Julian , Peacock Sharon J. , de Goffau Marcus C. , Wagner Josef , Harrison Ewan M.
Published: October 2023

16S rRNA gene sequencing is widely used to characterize human and environmental microbiomes. Sequencing at scale facilitates better powered studies but is limited by cost and time. We identified two areas in our 16S rRNA gene library preparation protocol where modifications could provide efficiency gains, including (1) pooling of multiple PCR amplifications per sample to reduce PCR drift and (2) manual preparation of mastermix to reduce liquid handling. Using nasal samples from healthy human participants and a serially diluted mock microbial community, we compared alpha and beta diversity, and compositional abundance where the PCR amplification was conducted in triplicate, duplicate or as a single reaction, and where manually prepared or premixed mastermix was used. One hundred and fifty-eight 16S rRNA gene sequencing libraries were prepared, including a replicate experiment. Comparing PCR pooling strategies, we found no significant difference in high-quality read counts and alpha diversity, and beta diversity by Bray–Curtis index clustered by replicate on principal coordinate analysis (PCoA) and non-metric dimensional scaling (NMDS) analysis. Choice of mastermix had no significant impact on high-quality read and alpha diversity, and beta diversity by Bray–Curtis index clustered by replicate in PCoA and NMDS analysis. Importantly, we observed contamination and variability of rare species (<0.01 %) across replicate experiments; the majority of contaminants were accounted for by removal of species present at <0.1 %, or were linked to reagents (including a primer stock). We demonstrate no requirement for pooling of PCR amplifications or manual preparation of PCR mastermix, resulting in a more efficient 16S rRNA gene PCR protocol.
The advantage of intergenic regions as genomic features for machine-learning-based host attribution of Salmonella Typhimurium from the USA
Authors: Chalka Antonia , Dallman Tim J. , Vohra Prerna , Stevens Mark P. , Gally David L.
Published: October 2023

Salmonella enterica

is a taxonomically diverse pathogen with over 2600 serovars associated with a wide variety of animal hosts including humans, other mammals, birds and reptiles. Some serovars are host-specific or host-restricted and cause disease in distinct host species, while others, such as serovar S. Typhimurium (STm), are generalists and have the potential to colonize a wide variety of species. However, even within generalist serovars such as STm it is becoming clear that pathovariants exist that differ in tropism and virulence. Identifying the genetic factors underlying host specificity is complex, but the availability of thousands of genome sequences and advances in machine learning have made it possible to build specific host prediction models to aid outbreak control and predict the human pathogenic potential of isolates from animals and other reservoirs. We have advanced this area by building host-association prediction models trained on a wide range of genomic features and compared them with predictions based on nearest-neighbour phylogeny. SNPs, protein variants (PVs), antimicrobial resistance (AMR) profiles and intergenic regions (IGRs) were extracted from 3883 high-quality STm assemblies collected from humans, swine, bovine and poultry in the USA, and used to construct Random Forest (RF) machine learning models. An additional 244 recent STm assemblies from farm animals were used as a test set for further validation. The models based on PVs and IGRs had the best performance in terms of predicting the host of origin of isolates and outperformed nearest-neighbour phylogenetic host prediction as well as models based on SNPs or AMR data. However, the models did not yield reliable predictions when tested with isolates that were phylogenetically distinct from the training set. The IGR and PV models were often able to differentiate human isolates in clusters where the majority of isolates were from a single animal source. Notably, IGRs were the feature with the best performance across multiple models which may be due to IGRs acting as both a representation of their flanking genes, equivalent to PVs, while also capturing genomic regulatory variation, such as altered promoter regions. The IGR and PV models predict that ~45 % of the human infections with STm in the USA originate from bovine, ~40 % from poultry and ~14.5 % from swine, although sequences of isolates from other sources were not used for training. In summary, the research demonstrates a significant gain in accuracy for models with IGRs and PVs as features compared to SNP-based and core genome phylogeny predictions when applied within the existing population structure. This article contains data hosted by Microreact.
Enhancing Mental Well-being: Efficacy and Neural Mechanisms of Leyi Training in Emotional and Cognitive Intervention
Authors: Jia Xiaofei , Li Rui , Zhou Changle
Published: October 2023

Leyi mental training comprises physical and mental cultivation methods, such as relaxation, breathing, meditation, koan, and cognitive regulation, with the ultimate goal of achieving enlightenment. Over a decade of practical experience has demonstrated its potential to enhance individuals’ mental well-being. In our study, we employed EEG and psychological scales to investigate the efficacy of Leyi training in emotional and cognitive intervention, as well as its underlying neural mechanisms. The results revealed significant improvements in both emotion and cognition following the intervention. We propose that the effectiveness of Leyi training in emotional regulation may stem from the heightened sensitivity to present experiences and the robust cognitive control ability cultivated through the practice, which enables practitioners to allocate equal, non-reactive attention to all stimuli, regardless of their emotional valence. Moreover, this training facilitates more effective allocation of cognitive resources to deal with current tasks, thus improving cognitive abilities.
Monitoring Resilience in Bursts
Authors: Delecroix Clara , van Nes Egbert H , Scheffer Marten , van de Leemput Ingrid A
Published: October 2023

The possibility to anticipate critical transitions through detecting loss of resilience has attracted attention in a variety of fields. Resilience indicators rely on the mathematical concept of critical slowing down, which means that a system recovers increasingly slowly from external perturbations when approaching a tipping point. This decrease in recovery rate can be reflected in rising autocorrelation and variance in data. To test whether resilience is changing, resilience indicators are often calculated using a moving window in long, continuous time series of the system. However, for some systems it may be more feasible to collect several high-resolution time series in short periods of time, i.e. in bursts. Resilience indicators can then be calculated to detect a change of resilience in a system between such bursts. Here, we compare the performance of both methods using simulated data, and showcase possible use of bursts in a case-study using mood data to anticipate depression in a patient. Using the same number of data points, the burst approach outperformed the moving window method, suggesting that it is possible to down-sample the continuous time series and still signal of an upcoming transition. We suggest guidelines to design an optimal sampling strategy. Our results imply that using bursts of data instead of continuous time series may improve the capacity to detect changes in systems’ resilience. This method is promising for a variety of fields, such as human health, epidemiology, or ecology, where continuous monitoring is costly or unfeasible.

Significance statement

Gauging the risk of tipping points is of great relevance in complex systems ranging from health to climate, and ecosystems. For this purpose, dynamical indicators of resilience are being derived from long continuous time series to monitor the system and obtain early warning signals. However, gathering such data is often prohibitively expensive or practically unfeasible. Here we show that collecting data in brief, intense bursts may often solve the problem, making it possible to estimate change in resilience between the bursts withrelatively high precision. This may be particularly useful for monitoring resilience of humans or animals, where brief time series of blood pressure, balance, mood or other relevant markers may be collected relatively easily to help estimating systemic resilience.
Behavioral Thermoregulation in Captive Fish: Molecular, Physiological, and Welfare Implications
Authors: Sanhueza Nataly , Fuentes Ricardo , Aguilar Andrea , Carnicero Beatriz , Mattos Humberto , Rubalcaba Yuniel , Melin Victoria , Contreras David , Boltana Sebastian
Published: October 2023

Environmental Enrichment (EE) serves as a cornerstone in the attempt to emulate natural habitats for captive organisms. While substantial strides have been made in this field, current methodologies still grapple with discrepancies between recreated habitats and the innate conditions vital for maintaining biological homeostasis in captive species. Our study highlights the pivotal role of behavioral thermoregulation in modulating molecular and physiological outcomes in captive fish. Collective evidence suggests that enabling fish to autonomously regulate temperature confers numerous beneficial cellular and systemic effects. Specifically, introducing a thermal gradient within the EE paradigm correlated with increased survival metrics, enhanced physiological parameters, and improved welfare indices, establishing the criticality of thermoregulation in captivity. In contrast, the lack of a thermoregulatory framework resulted in the emergence of transient free radicals, a clear marker of temperature-induced oxidative stress. Persistent disruptions in free radical equilibrium, especially in uniform temperature settings, were linked to DNA damage, heightened cellular apoptosis, tissue anomalies, and metabolic deviations. In conclusion, this research underscores the significance of behavioral thermoregulation as an integral feature of EE, especially related to fish in controlled environments. Our data present key biomarkers valuable for optimizing fish welfare and highlight the necessity for sustained research into their adaptability and survival benchmarks. Such insights aim to enhance EE protocols, fortifying their efficacy in mirroring natural habitats and, in turn, advancing the welfare benchmarks of captive organisms.
Quantifying massively parallel microbial growth with spatially mediated interactions
Authors: Borse Florian , Kičiatovas Dovydas , Kuosmanen Teemu , Vidal Mabel , Cabrera-Vives Guillermo , Cairns Johannes , Warringer Jonas , Mustonen Ville
Published: October 2023

Quantitative understanding of microbial growth is an essential prerequisite for successful control of pathogens as well as various biotechnology applications. Even though the growth of cell populations has been extensively studied, microbial growth remains poorly characterized at the spatial level. Indeed, even isogenic populations growing at different locations on solid growth medium typically show significant location-dependent variability in growth. Here we show that this variability can be attributed to an interplay between populations interacting with their local environment and the diffusion of nutrients and energy sources coupling the environments, i.e. interpopulation interactions are mediated via the shared environment. We use a dual approach, first applying machine learning regression models to discover that location dominates growth variability at specific times, and, in parallel, developing explicit population growth models to describe this spatial effect. In particular, treating nutrient and energy source concentration as a latent variable allows us to develop a mechanistic resource consumer model that captures growth variability across the shared environment. As a consequence, we are able to determine intrinsic growth parameters for each local population, removing confounders common to location-dependent variability in growth. Importantly, our explicit low parametric model for the environment paves the way for massively parallel experimentation with configurable spatial niches for testing specific eco-evolutionary hypotheses.

Author summary

Image-based platforms allow obtaining population size estimates for massively parallel growth experiments on substrate plates at relatively low cost. However, such population size data has been shown to display a high degree of spatial variability, which occurs even with isogenic populations.

Here we first quantified the importance of spatial location on growth variation using a machine learning approach, and then developed spatially aware population growth models to explain the spatial structure of the growth data. Ultimately, we showed that a spatial consumer-resource model with local microhabitats connected via diffusion can fully explain the observed spatial variation in growth while allowing the inference of intrinsic growth parameters of specific populations.

This result provides a method for systematic extraction of spatial growth models and paves the way for massively parallel eco-evolutionary experimentation.
‘If you find that I am HIV Positive, Don’t Tell me’: Exploring the barriers and recommendations for HIV Prevention services utilization among youth in rural southwestern Uganda
Authors: Ssali Paul Waswa , Kintu Timothy Mwanje , Karungi Immaculate , Namuyaba Agnes Kisakye , Kyagambiddwa Tonny , Namaseruka Ruth , Agaba Mark , Obua Celestino , Wakida Edith K , Kabakyenga Jerome Kahuma
Published: October 2023

Background

Globally, the majority of new HIV infections are recorded in Eastern and Southern Africa, with the youth being disproportionately affected. HIV prevention is the cornerstone of controlling the spread of HIV and ending this epidemic by 2030. However, barriers to the utilization of HIV prevention services have not been extensively explored among the youth in rural settings in sub-Saharan Africa. This study explored these barriers and identified recommendations to improve the utilization of HIV prevention methods among youth in rural southwestern Uganda.

Methods

This was a qualitative study done in the Rubirizi district in southwestern Uganda between February and April 2022. We conducted six Focus Group Discussions (with youth [15-24 years] both in and out of school), nine in-depth interviews (with teachers, health workers, and members of the village health team), and four key informant interviews (with district officials) to collect data. Thematic analysis was done to identify the barriers to and establish recommendations for the utilization of HIV prevention services from the study participants. Both deductive and inductive approaches were used during the analysis.

Results

The identified barriers were categorized into individual barriers (ignorance and misconceptions about the services, fear of testing, low perceived susceptibility to HIV, and fear of breach of confidentiality), community barriers (lack of counseling services in the communities, peer influence, and stigma towards HIV), and a health system barrier (lack of youth-friendly services). Three main recommendations were established including the formation of youth peer support groups, ongoing awareness campaigns, and socio-economic empowerment.

Conclusion

There’s a need for national scaling of awareness campaigns and sexual and reproductive health services, such as youth peer support services to address most of the identified barriers. Additionally, economic empowerment especially among adolescent girls and young women has enormous potential to address the spread of HIV in this sub-population.
Structural and functional features characterizing the brains of individuals with higher controllability of motor imagery
Authors: Furuta Tomoya , Morita Tomoyo , Miura Gen , Naito Eiichi
Published: October 2023

Motor imagery is a higher-order cognitive brain function that mentally simulates movements without performing the actual physical one. Although many studies have dealt with motor imagery, neural bases that determine individual differences in motor imagery ability are not well understood. Using magnetic resonance imaging and controllability of motor imagery (CMI) test that can objectively evaluate individual ability to manipulate one’s imaginary postures, we show that the bilateral superior frontoparietal white matter region expands in higher CMI test scorers. In addition, CMI test activates the bilateral dorsal premotor cortex (PMD) and superior parietal lobule (SPL); specifically, the left PMD and/or the right SPL enhance functional coupling with the visual body, somatosensory, and motor/kinesthetic areas in the higher scorers. This study elucidated the structural and functional features that characterize the brains of individuals with higher controllability of motor imagery, and advanced understanding of individual differences in motor imagery ability.
Peripherally derived LGI1-reactive monoclonal antibodies cause epileptic seizuresin vivo
Authors: Upadhya Manoj , Kirmann Toni , Wilson Max , Simon Christian M , Dhangar Divya , Geis Christian , Williams Robyn , Woodhall Gavin , Hallermann Stefan , Irani Sarosh R , Wright Sukhvir K
Published: October 2023

One striking clinical hallmark in patients with autoantibodies to leucine-rich glioma inactivated 1 (LGI1) is the very frequent focal seizure semiologies, including faciobrachial dystonic seizures (FBDS), in addition to the amnesia. Polyclonal serum IgGs have successfully modelled the cognitive changesin vivobut not seizures. Hence, it remains unclear whether LGI1-autoantibodies are sufficient to cause seizures.

We tested this with the molecularly precise monoclonal antibodies directed against LGI1 (LGI1-mAbs), derived from patient circulating B cells. These were directed towards both major domains of LGI1, LRR (n=5) and EPTP (n=5) and infused intracerebroventricularly over 7 days into juvenile male Wistar rats using osmotic pumps. Continuous wireless EEG was recorded from a depth electrode placed in hippocampal CA3 plus behavioural tests for memory and hyperexcitability were performed. Following infusion completion (Day 9), post-mortem brain slices were studied using electrophysiology and immunostaining.

By comparison to control-mAb injected rats (n=6), video-EEG analysis over 9 days revealed convulsive and non-convulsive seizure activity in rats infused with LGI1-mAbs, with a significant number of ictal events (245±83 vs. 7.8±7.8 in controls; p=0.002). Memory was not impaired in the novel object recognition test. Local field potential recordings from postmortem brain slices showed spontaneous ictal-like spike activity in the CA3 region (p=0.03). The LGI1-mAbs bound most strongly in the hippocampal CA3 region and induced a significant reduction in Kv1.1 cluster number in this subfield (6 controls; 7 LGI1-mAbs; p=0.01)

Peripherally-derived human LGI1-mAbs infused into rodent CSF provide strong evidence of directin vivoepileptogenesis with molecular correlations. These findings fulfill criteria for LGI1-antibodies in seizure causation.
Rationalised experiment design for parameter estimation with sensitivity clustering
Authors: Chhajer Harsh , Roy Rahul
Published: October 2023

Quantitative experiments are essential for investigating, uncovering and confirming our understanding of complex systems, necessitating the use of effective and robust experimental designs. Despite generally outperforming other approaches, the broader adoption of model-based design of experiments (MBDoE) has been hindered by oversimplified assumptions and computational overhead. To address this, we present PARameter SEnsitivity Clustering (PARSEC), an MBDoE framework that identifies informative measurable combinations through parameter sensitivity (PS) clustering. We combined PARSEC with a new variant of Approximate Bayesian Computation for rapid, automated assessment and ranking of designs. By inherent design, PARSEC can take into account experimental restrictions and parameter variability. We show that PARSEC improves parameter estimation for two different types of biological models. Importantly, PARSEC can determine the optimal sample size for information gain, which we show correlates well with the optimal number of PS clusters. This supports our rationale for PARSEC and demonstrates the potential to harness both model structure and system behaviour to efficiently navigate the experiment design space.