bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing incidence and risk factors of laparoscopic cholecystectomy complications in Jeddah: a retrospective study
Authors: AlKhalifah Zainab , Alzahrani Amal , Abdu Shahad , Kabbarah Ammar , Kamal Omar , Althoubaity Fatma
Published: May 2023

Context:

Laparoscopic cholecystectomy (LC) is the gold standard treatment for gallstones. However, it is associated with several complications. No previous studies have investigated LC complications and their associated risk factors in the western region of Saudi Arabia.

Aims:

We aimed to identify the risk factors for postoperative complications (POCs) of LC at a tertiary institute in Jeddah, Western Saudi Arabia.

Settings and design:

This retrospective study was conducted between June 2021 and August 2021 among patients who underwent LC at a tertiary centre in Jeddah, Saudi Arabia.

Materials and methods:

Records of 596 patients were reviewed, and 510 patients were included in the final analysis after applying the exclusion criteria. Data were collected from hospital medical records. χ
2 tests and independent t tests were used to analyse categorical and continuous variables, respectively. The Mann–Whitney U test was used for nonparametric data. Multivariate regression analysis was used to adjust the P values to determine the most strongly and independently associated risk factors.

Results:

Our data showed that the overall incidence of intraoperative complications (IOCs) was 10.8%. The most common complications were gallbladder perforation (n=28, 5.5%), bile leakage (n=25, 4.9%), and bleeding (n=15, 2.9%). POCs occurred in 11% of the patients; the majority complained of abdominal pain (n=36, 6.9%), had elevated liver function tests (n=14, 2.7%), and retained stones (n=11, 2.2%). Acute cholecystitis, overweight, diabetes, and male sex were significant predictors of IOC, POC, and conversion to open cholecystectomy (P<0.05).

Conclusions:

LC complications have a multifactorial aetiology. Patient awareness of all possible IOCs is fundamental. The improved skill and experience of the surgical team can mitigate serious complications.
Ultrasound vs. clinical diagnosis—which is better in diagnosing acute appendicitis?: a cohort study
Authors: Kam Cheuk Tung , Alsahaf Mahdi , Chongbang Kul , Taki Mona , Yusob Jamal , Alexander Santhosh , Rait Jaideep
Published: May 2023

Background:

Acute appendicitis is one of the most common causes of right iliac fossa pain which often warrants surgical management. In many cases, abdominal ultrasonography (USS) is done to confirm the diagnosis however negative appendicectomy is common due to atypical presentations and different visualisation rate. The unnecessary operative intervention can result in complications. The aim of this study was to compare the efficacy between clinical diagnosis and USS in diagnosing acute appendicitis to avoid negative appendicectomy and prevent further complications.

Method:

A retrospective cohort study was conducted in a district general hospital which 1046 cases of laparoscopic appendicectomy were included and examined for the use of USS or clinical diagnosis. The sensitivity, specificity, negative and positive predictive value in USS and data in clinical evaluation were analysed for their accuracy in the diagnosis of acute appendicitis based on the histology results post appendicectomy.

Results:

Clinical diagnosis without preoperative imaging was found to have a significantly lower negative appendicectomy rate of 27.20% compared with 42.67% in those who underwent ultrasound. 44.64% of the patients were misdiagnosed with a normal USS result who had a subsequent positive histology of appendicitis.

Conclusions:

USS has been shown to be less sensitive for diagnosing acute appendicitis which results in high negative appendicectomy and misdiagnosis rate. With an increasing burden of health budget and resources, cautious and appropriate use of USS would avoid the misdiagnosis and prevent further complications. Thorough clinical evaluation remains an important first step and role in the diagnosis of acute appendicitis.
Intraosseous angiolipoma of the humerus: a second case report
Authors: Khana Firas K. , Khabbak Sina , Shaikh Torab Sana , Arslan Mohammed W. , Mouhandes Mohamed I.E.
Published: May 2023

Introduction and Importance:

To document a case of an intraosseous angiolipoma (IOAL) of the humerus.

Case presentation:

A 52-year-old woman presented with gradually increasing pain in her right arm. A X-ray series of the right elbow and computed tomography revealed a nonexpanding radiolucent lesion in the distal end of the right humerus. The fatty nature of the lesion was further verified using fat-suppression techniques on magnetic resonance imaging sequences.

Clinical discussion:

The tumor was surgically excised, and the patient has experienced no symptoms for 2 years now. Histopathological findings confirmed the presence of an IOAL, which is an extremely rare intraosseous tumor that consists of thin blood vessels and mature adipose tissue.

Conclusion:

Accurate diagnosis of an IOAL is challenging; therefore, careful planning and assessment are paramount in the management of such lesions, with histological findings being essential for a conclusive diagnosis and surgery is the most suitable treatment choice in most cases.
Dreadful infectious disease outbreaks threaten flood-ravaged pakistan: short communication
Authors: Shaikh Omer Ahmed , Rahim Maliha , Essarani Manisha , Nadeem Soeba , Ochani Sidhant , Hasibuzzaman Md. Al , Ullah Kaleem
Published: May 2023

A rise in the incidence of water-borne, communicable illnesses, and viral outbreaks in Pakistan follows periods of heavy rainfall. Due to climate change, floods and droughts have had devastating effects on human health by facilitating the spread of infectious illnesses including cholera, malaria, typhoid, dengue fever, and viral hepatitis A. Food instability, starvation, malnutrition, and a lack of potable water are only some of the indirect effects of flooding on health. Recently, one of the worst floods in history devastated Pakistan, affecting more than 333 million people along with a significant portion of the nation submerged. Malaria, dengue fever, and other ailments are on the rise in Pakistan, threatening to overwhelm the country’s healthcare infrastructure. There is an urgent need for preventative measures in Pakistan to cope with dreadful outbreaks.
Utility of neutrophil to lymphocyte ratio to predict acute respiratory distress syndrome in COVID-19: short communication
Authors: Bano Mehdi Kulsoom , Jehan Shahzeeba , Akhter Madiha , Angez Meher , Nasir Nosheen
Published: May 2023

Background:

Acute respiratory distress syndrome (ARDS) is the most severe and devastating form of acute lung injury. Neutrophil to lymphocyte ratio (NLR) and C-reactive protein have been used to predict severity and prognosis of certain viral illnesses.

Methods:

A retrospective cohort study was conducted in hospitalized COVID-19 patients. Serial measurements of NLR and C-reactive protein were recorded and patients were followed for development of ARDS.

Results:

Out of 388 patients admitted with COVID-19, 43 patients developed ARDS compared with 345 patients who did not develop ARDS. The median NLR at presentation was significantly higher in patients who developed ARDS (8.89 vs. 4.25) compared with those who did not develop ARDS (P<0.001). Moreover, serial measurement of NLR at presentation, day 3, day 5 and day 7 was significantly associated with development of ARDS (P<0.001). In multivariable analysis, age of greater than or equal to 50 years (adsjusted odds ratio=3.28; 95% CI=1.40–7.69) and unit increase in NLR at presentation (adsjusted odds ratio=1.07; 95% CI=1.03–1.11) were independently associated with development of ARDS.

Conclusion:

Serial measurement of NLR can predict patients who are at a greater risk for developing ARDS in COVID-19.
Degree of kidney injury due to artificial pelvic-ureteric junction obstruction with level of neutrophil gelatinase-associated lipocalin, interleukin 18, and histopathological descriptions in Wistar: experimental research
Authors: Sigumonrong Yacobda Hamonangan , Dharmajaya Ridha , Warli Syah Mirsya , Eyanoer Putri Chairani , Wahyudi Irfan , Sembiring Rosita Juwita , Alferraly Tengku Ibnu , Rusda Muhammad
Published: May 2023

Background:

Pelvic-ureteric junction obstruction (PUJO) is considered the most common pathology for hydronephrosis in neonates. Full recovery of kidney impairment due to PUJO is possible, especially when pyeloplasty is indicated as surgery is mostly conducted when deterioration is identified, early detection should be considered to prevent further complications. Commonly used kidney damage biomarkers are not sensitive enough to predict kidney damage. Neutrophil gelatinase-associated lipocalin (NGAL) and urinary interleukin 18 (IL-18) are markers of early kidney damage with different characteristics. This study aimed to evaluate the relationship between these two markers with the degree of histopathological kidney damage in Wistar rats induced by PUJO.

Methods:

A total of thirty male Wistar rats, 200–250 g, were divided into three groups: (1) control, (2) sham, (3) PUJO (4th, 7th, 14th, and 21st days). Urine NGAL, IL-18 levels, and renal histopathology were observed on day 0, 4, 7, 14, and 21. Statistical analysis was performed using the Kruskal–Wallis and Mann–Whitney test with P less than 0.05 considered significant.

Results:

There was no significant difference in urine NGAL levels between groups, while IL-18 levels were significantly different based on the Kruskal–Wallis test (P 0.031). The results of the Mann–Whitney test showed a significant difference in IL-18 levels between the control group and the PUJO group on day 4 (P=0.028); the Sham surgery group with the PUJO group on day 4 (P=0.014); the PUJO group on day 4 with the PUJO group on the 7th day (P=0.008); and the PUJO group on the 7th day with the PUJO group on the 14th day (P=0.033).

Conclusion:

Urinary IL-18 levels can be used as a predictor of kidney damage in acute-subacute PUJO cases.
67Ga-PSMA I&T for Radioguided Surgery of Lymph Node Metastases in Patients With Biochemical Recurrence of Prostate Cancer
Authors: Winkens Thomas , Berger Frank Peter , Foller Susan , Greiser Julia , Groeber Sebastian , Grimm Marc-Oliver , Freesmeyer Martin , Kuehnel Christian
Published: May 2023

Purpose

Radioguided lymph node dissection in patients with prostate cancer, and suffering from biochemical recurrence has been described thoroughly during the past few years. Several prostate-specific membrane antigen (PSMA)–directed ligands labeled with 111In, 99mTc, and 68Ga have been published; however, limitations regarding availability, short half-life, high costs, and unfavorable high energy might restrict frequent use. This study aims at introducing 67Ga as a promising radionuclide for radioguided surgery.

Methods

Retrospective analysis was performed on 6 patients with 7 PSMA-positive lymph node metastases. 67Ga-PSMA I&T (imaging and therapy) was synthesized in-house and intravenously applied according to §13 2b of the German Medicinal Products Act. Radioguided surgery was performed 24 hours after injection of 67Ga-PSMA I&T using a gamma probe. Patient urine samples were collected. Occupational and waste dosimetry was performed to describe hazards arising from radiation.

Results

67Ga-PSMA application was tolerated without adverse effects. Five of 7 lymph nodes were detected on 22-hour SPECT/CT in 4 of 6 patients. During surgery, all 7 lymph node metastases were identified by positive gamma probe signal. Relevant accumulation of 67Ga was observed in lymph node metastases (32.1 ± 15.1 kBq). Histology analysis of near-field lymph node dissection revealed more lymph node metastases than PET/CT (and gamma probe measurements) identified. Waste produced during inpatient stay required decay time of up to 11 days before reaching exemption limits according to German regulations.

Conclusions

Radioguided surgery using 67Ga-PSMA I&T is a safe and feasible option for patients suffering from biochemical recurrence of prostate cancer. 67Ga-PSMA I&T was successfully synthesized according to Good Manufacturing Practice guidelines. Radioguided surgery with 67Ga-PSMA I&T does not lead to relevant radiation burden to urology surgeons and represents a novel interdisciplinary approach in nuclear medicine and urology.
Stem Cell–Enriched Fat Grafts Versus Autologous Fat Grafts for Facial Reconstruction
Authors: Karam Mohammad , Abul Ahmad , Wood Benjamin , Kahlar Narvair , Naik Anish , Tay Jing , Rahman Shafiq , Matteucci Paolo
Published: May 2023

Objective

The aim of the study is to compare the outcomes of stem cell-enrichment fat grafting versus routine fat grafting for facial reconstruction purposes.

Methods

A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses Guidelines and a search of electronic information was conducted to identify all randomized controlled trials, case control studies, and cohort studies comparing the outcomes of stem cell enrichment fat grafting versus routine fat grafting for facial reconstruction purposes. Volume retention and infection rate were primary outcome measures. Secondary outcome measures included patient satisfaction postsurgery, redness and swelling, fat necrosis, cysts, as well as operation time. Fixed and random effects modeling was used for the analysis.

Results

Eight studies enrolling 275 subjects were selected. There was a significant difference between the stem cell enrichment fat grafting and routine grafting groups in terms of mean volume retention (standardized mean difference, 2.49; P < 0.00001). However, there was no significant difference between the 2 groups in the rate of infection (odds ratio, 0.36; P = 0.30). For all secondary outcomes, the intervention group had similar results compared with the control group except for the operation time, which was shorter in the latter.

Conclusions

Stem cell–enriched fat grafting is a superior option when compared with the routine fat grafting for facial reconstruction surgery because it improves the mean volume retention and does not worsen patient satisfaction and surgical complications.
Single-Use Negative Pressure Wound Therapy Applied on Various Wound Types
Authors: Amin Neha , Homsombath Bounthavy , Rumbaugh John , Craft-Coffman Beretta , Fagan Shawn P. , Chowdhry Tayseer , Wilson Joan , Paglinawan Rey , Lussi Karin , Hassan Zaheed
Published: May 2023

PURPOSE:

The purpose of this study was to determine whether a single-use negative pressure wound therapy (NPWT) system achieves individualized goals of therapy when used to treat patients with a variety of wound types.

DESIGN:

Multiple case series.

SUBJECTS AND SETTING:

The same comprised 25 participants; their mean age was 51.2 years (SD: 18.2; range: 19-79 years); 14 were male (56%) and 11 were female (44%). Seven study participants withdrew from study participation. Wound etiologies vary; 4 had diabetic foot ulcers; 1 had a full-thickness pressure injury; 7 were treated for management of an abscess or cyst; 4 had necrotizing fasciitis, 5 had nonhealing postsurgical wounds, and 4 had wounds of other etiologies. Data were collected at 2 ambulatory wound care clinics located in the Southeastern United States (Augusta and Austell, Georgia).

METHODS:

A single-outcome measure was selected for each participant by his or her attending physician at a baseline visit. Selected end points were (1) decrease in wound volume, (2) decrease in size of the tunneling area, (3) decrease in size of the undermining, (4) decrease in the amount of slough, (5) increase in granulation tissue formation, (6) decrease in periwound swelling, and (7) wound bed progression toward transition to another treatment modality (such as standard dressing, surgical closure, flap, or graft). Progress toward the individualized goal was monitored until the goal was achieved (study end point) or a maximum of 4 weeks following initiation of treatment.

RESULTS:

The most common primary treatment goal was to achieve a decrease in wound volume (22 of 25 study participants), and the goal to increase granulation tissue was chosen for the remaining 3 study participants. A majority of participants (18 of 23, 78.3%) reached their individualized treatment outcome. The remaining 5 participants (21.7%) were withdrawn during the study (for reasons not related to the therapy). The median (interquartile range [IQR]) duration of NPWT therapy was 19 days (IQR: 14-21 days). Between baseline and the final assessment, median reductions in wound area and volume were 42.7% (IQR: 25.7-71.5) and 87.5% (IQR: 30.7-94.6).

CONCLUSIONS:

The single-use NPWT system achieved multiple individualized treatment objectives in a variety of wound types. Individually selected goals of therapy were met by all study participants who completed the study.
Hospital-Acquired Pressure Injuries in Adults With Prone Positioning Using Manual Method Versus Specialty Bed
Authors: DeMellow Jacqueline M. , Dhillon Harbir , Bhattacharyya Mouchumi , Pacitto Daniel , Kozik Teri M.
Published: May 2023

PURPOSE:

The purpose of this study was to compare the incidence of hospital-acquired pressure injuries (HAPIs) in patients with acute respiratory distress syndrome (ARDS) and placed in a prone position manually or using a specialty bed designed to facilitate prone positioning. A secondary aim was to compare mortality rates between these groups.

DESIGN:

Retrospective review of electronic medical records.

SUBJECTS AND SETTING:

The sample comprised 160 patients with ARDS managed by prone positioning. Their mean age was 61.08 years (SD = 12.73); 58% (n = 96) were male. The study setting was a 355-bed community hospital in the Western United States (Stockton, California). Data were collected from July 2019 to January 2021.

METHODS:

Data from electronic medical records were retrospectively searched for the development of pressure injuries, mortality, hospital length of stay, oxygenation status when placed in a prone position, and the presence of a COVID-19 infection.

RESULTS:

A majority of patients with ARDS were manually placed in a prone position (n = 106; 64.2%), and 54 of these patients (50.1%) were placed using a specialty care bed. Slightly more than half (n = 81; 50.1%) developed HAPIs. Chi-square analyses showed no association with the incidence of HAPIs using manual prone positioning versus the specialty bed (P = .9567). Analysis found no difference in HAPI occurrences between those with COVID-19 and patients without a coronavirus infection (P = .8462). Deep-tissue pressure injuries were the most common type of pressure injury. More patients (n = 85; 80.19%) who were manually placed in a prone position died compared to 58.18% of patients (n = 32) positioned using the specialty bed (P = .003).

CONCLUSIONS:

No differences in HAPI rates were found when placing patients manually in a prone position versus positioning using a specialty bed designed for this purpose.
Alternate inks for arbuscular mycorrhizal root staining
Authors: Wilkes Thomas I
Published: May 2023

Alternate methods for root staining of arbuscular mycorrhizal (AM) fungi have recently gained more attention for the reduction of hazard exposure to the user. Sheaffer® blue ink has been employed for such an identification and quantification, having shown and increased degree of image clarity. However, sourcing Sheaffer® blue ink is becoming problematic, leading to the need to find alternative inks that are readily available. Parker® ink is a well-known brand, providing comparable colour option to Sheaffer®. Two Parker® inks, blue and washable blue, were employed alongside Sheaffer® blue for comparative AM fungal root staining. From quantified AM fungal vesicles and arbuscles, along with the degree of stained image clarity under microscopy, none of the inks utilised for this comparison produce a significantly (P=0.97) different AM fungal quantification or change in image clarity. Therefore, results of the present communication suggest that Parker® blue and washable blue inks are alternative ink stains for the viewing and quantification of AM fungi in host cortical root tissues.
Meropenem resistant Burkholderia pseudomallei - A concerning single case in Australia with no prior meropenem exposure
Authors: Sivabalan Pirathaban , Satyaputra Ferris , Gassiep Ian , Forde Brian , Frazer Jaimie , Glover Matthew , Adams Buenafe , Norton Robert
Published: May 2023

We report a case of cutaneous melioidosis in a 54-year-old male with a meropenem resistant sub-population. He was empirically treated with episodic doxycycline and trimethoprim-sulfamethoxazole, however the abscess re-accumulated. The patient had no prior exposure to meropenem. A sub-population of the isolate was meropenem resistant with an MIC>32 µg/ml and the identification was re-confirmed as B. pseudomallei. Whole genome sequencing with ARDaP analysis only revealed a resistance determinant to doxycycline. It didn’t reveal a resistance determinant to meropenem. Furthermore, no carbapenemases were detected through the Abricate program, using both CARD and ResFinder databases. To date this is the first reported case in Australia of a B. pseudomallei isolate resistant to meropenem without previous carbapenem exposure.
Gramella oceanisediminis sp. nov., isolated from deep-sea sediment of the Indian Ocean
Authors: Yang Lin , Shi Haolei , Li Qian , Zheng Minggang , Lai Qiliang , Zheng Li
Published: May 2023

A taxonomic study was carried out on strain GC03-9T, which was isolated from deep-sea sediment of the Indian Ocean. The bacterium was Gram-stain-negative, catalase-positive, oxidase-negative, rod-shaped and gliding motile. Growth was observed at salinities of 0–9 % and at temperatures of 10–42 °C. The isolate could degrade gelatin and aesculin. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain GC03-9T belonged to the genus

Gramella

, with the highest sequence similarity to

Gramella bathymodioli

JCM 33424T (97.9 %), followed by

Gramella jeungdoensis

KCTC 23123T (97.2 %) and other species of the genus

Gramella

(93.4–96.3 %). The average nucleotide identity and the digital DNA–DNA hybridization estimate values between strain GC03-9T and

G. bathymodioli

JCM 33424T and

G. jeungdoensis

KCTC 23123T were 25.1 and 18.7 % and 82.47 and 75.69 %, respectively. The principal fatty acids were iso-C15 : 0 (28.0 %), iso-C17 : 0 3OH (13.4 %), summed feature 9 (iso-C17 : 1
 ω9c and/or 10-methyl C16 : 0; 13.3 %) and summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c; 11.0 %). The G+C content of the chromosomal DNA was 41.17 mol%. The respiratory quinone was determined to be menaquinone-6 (100 %). Phosphatidylethanolamine, one unknown phospholipid, three unknown aminolipids and two unknown polar lipids were present. The combined genotypic and phenotypic data showed that strain GC03-9T represents a novel species within the genus

Gramella

, for which the name Gramella oceanisediminis sp. nov. is proposed, with the type strain GC03-9T (=MCCC M25440T=KCTC 92235T).
Exploring the genetic heterogeneity of Alzheimer’s disease: Evidence for genetic subtypes
Authors: Elman Jeremy A. , Schork Nicholas J. , Rangan Aaditya V. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2023

Background

Alzheimer’s disease (AD) exhibits considerable phenotypic heterogeneity, suggesting the potential existence of subtypes. AD is under substantial genetic influence, thus identifying systematic variation in genetic risk may provide insights into disease origins.

Objective

We investigated genetic heterogeneity in AD risk through a multi-step analysis.

Methods

We performed principal component analysis (PCA) on AD-associated variants in the UK Biobank (AD cases=2,739, controls=5,478) to assess structured genetic heterogeneity. Subsequently, a biclustering algorithm searched for distinct disease-specific genetic signatures among subsets of cases. Replication tests were conducted using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset (AD cases=500, controls=470). We categorized a separate set of ADNI individuals with mild cognitive impairment (MCI; n=399) into genetic subtypes and examined cognitive, amyloid, and tau trajectories.

Results

PCA revealed three distinct clusters (‘constellations’) driven primarily by different correlation patterns in a region of strong LD surrounding theMAPTlocus. Constellations contained a mixture of cases and controls, reflecting disease-relevant but not disease-specific structure. We found two disease-specific biclusters among AD cases. Pathway analysis linked bicluster-associated variants to neuron morphogenesis and outgrowth. Disease-relevant and disease-specific structure replicated in ADNI, and bicluster 2 exhibited increased CSF p-tau and cognitive decline over time.

Conclusions

This study unveils a hierarchical structure of AD genetic risk. Disease-relevant constellations may represent haplotype structure that does not increase risk directly but may alter the relative importance of other genetic risk factors. Biclusters may represent distinct AD genetic subtypes. This structure is replicable and relates to differential pathological accumulation and cognitive decline over time.
Human norovirus (HuNoV) GII RNA in wastewater solids at 145 United States wastewater treatment plants: Comparison to positivity rates of clinical specimens and modeled estimates of HuNoV GII shedders
Authors: Boehm Alexandria B. , Wolfe Marlene K. , White Bradley , Hughes Bridgette , Duong Dorothea , Banaei Niaz , Bidwell Amanda
Published: May 2023

Background

Human norovirus (HuNoV) is a leading cause of disease globally, yet actual incidence is unknown. HuNoV infections are not reportable in the United States, and surveillance is limited to tracking severe illnesses or outbreaks. Wastewater monitoring for HuNoV has been done previously and results indicate it is present in wastewater influent and concentrations are associated with HuNoV infections in the communities contributing to wastewater. However, work has mostly been limited to monthly samples of liquid wastewater at one or a few wastewater treatment plants (WWTPs).

Objective

The objectives of this study are to investigate whether HuNoV GII preferentially adsorbs to wastewater solids, investigate concentrations of HuNoV GII in wastewater solids in wastewater treatment plants across the county, and explore how those relate to clinical measures of disease occurrence. In addition, we aim to develop and apply a mass-balance model that predicts the fraction of individuals shedding HuNoV in their stool based on measured concentrations in wastewater solids.

Methods

We measured HuNoV GII RNA in matched wastewater solids and liquid influent in 7 samples from a WWTP. We also applied the HuNoV GII assay to measure viral RNA in over 6000 wastewater solids samples from 145 WWTPs from across the United States daily to three times per week for up to five months. Measurements were made using digital droplet RT-PCR.

Results

HuNoV GII RNA preferentially adsorbs to wastewater solids where it is present at 1000 times the concentration in influent. Concentrations of HuNoV GII RNA correlate positively with clinical HuNoV positivity rates. Model output of the fraction of individuals shedding HuNoV is variable and uncertain, but consistent with indirect estimates of symptomatic HuNoV infections in the United States.

Significance

These findings support the utility of wastewater solids as a matrix for community infectious disease surveillance.

Impact Statement

Illness caused by HuNoV is not reportable in the United States so there is limited data on disease occurrence. Wastewater monitoring can provide information about the community spread of HuNoV. Data from wastewater can be available within 24 hours of sample receipt at a laboratory. Wastewater is agnostic to whether individuals seek medical care, are symptomatic, and the severity of illness. Knowledge gleaned from wastewater may be used by public health professionals to make recommendations on hand washing, surface disinfection, or other behaviors to reduce transmission of HuNoV, or medical doctors to inform clinical decision making.
The pleiotropic contribution of genes in dopaminergic and serotonergic pathways to addiction, aggression, and related behavioural traits
Authors: Antón-Galindo Ester , Cabana-Domínguez Judit , Torrico Bàrbara , Corominas Roser , Cormand Bru , Fernàndez-Castillo Noèlia
Published: May 2023

Co-occurrence of substance use disorders (SUD) and aggressive behaviour in the same individual has been frequently described. As dopamine (DA) and serotonin (5-HT) are key neurotransmitters for both phenotypes, we explored the genetic contribution of these pathways to SUD, aggressive behaviour and related behavioural traits. Here, we tested the association of 275 dopaminergic genes and 176 serotonergic genes with these phenotypes by performing gene-based, gene-set and transcriptome-wide association studies (TWAS) in 11 genome-wide association studies (GWAS) datasets on SUD (alcohol, cocaine, cannabis, opioids and a multivariate analysis of three drugs of abuse), aggressive behaviour (disruptive behaviour and antisocial behaviour) and related behaviours (irritability, neuroticism, risk taking and anxiety). At the gene-wide level, 68 DA and 27 5-HT genes were found to be associated with at least one GWAS on SUD or related behaviour. Among them, six genes had a pleiotropic effect, being associated with at least three phenotypes:ADH1C, ARNTL, CHRNA3, HPRT1, HTR1BandDRD2, the latter with five. Additionally, we found nominal associations between the DA gene sets and antisocial behaviour, opioid use disorder, SUD, irritability and neuroticism, and between the 5-HT-core gene set and neuroticism. Gene expression correlates in brain were also found for 19 genes, highlighting the association forCHRNA3andCELSR3with OUD, SUD and irritability andCELSR3also with neuroticism. Our study shows a pleiotropic contribution of dopaminergic and serotonergic genes to addiction, aggression and related behaviours, highlighting a special role for DA genes, which could explain, in part, the co-occurrence of these phenotypes.
Major UK non-commercial sponsors’ efforts to reduce research waste: a mixed methods study
Authors: Bruckner Till , Schuster Aminul , Chavarría Belén , Cruz Carolina , Lizárraga Karely , Borana Ronak , Bvute Tungamirai Ishe , Sánchez Daniel
Published: May 2023

This study provides a snapshot of the scale of legacy research waste in the UK. It assesses the current publication status of 145 clinical trials sponsored by ten major UK non-commercial sponsors that were completed or terminated in 2017. Following outreach to sponsors and short-term follow-up, 116/145 trials (80%) had fully reported results, and 11/145 trials (8%) had reported results in the grey literature. Results for 18/145 trials (12%) that enrolled 637 people remained completely unpublished as of early March 2023. Sponsors indicated that they plan to make public the results of 14/18 unreported trials. Our study had an impact on accelerating the reporting of some results, and seems likely to lead to future reductions in research waste. We propose three changes to UK Health Research Authority policies that could improve clinical trial reporting.
Risk factors for acne scarring in Ecuador
Authors: Camacho Mikaela , Viteri María Isabel , Yepez Paola , Porter Jorge Estrella , Belhadi Drifa , Barnes Caroline , Guillemot Jonathan
Published: May 2023

Background

Acne is a common disease that causes a large global disease burden. The Global Burden of Skin Disease reported that in 188 countries the burden from acne as measured by disability-adjusted life years (DALYs), years lived with disability and years of life lost is greatest in Western Europe, high-income North America and Southern Latin America. This paper aims to identify risk factors for acne scarring specific to the Ecuadorian population in order to adapt the 4-ASRAT tool accordingly.

Methods

This was an observational prospective study. Participants were recruited to complete a survey that was developed based on the potential risk factors for acne scarring and had facial photographs taken. To determine risk factors and their respective weighting, a logistic regression was performed.

Results

The study included 404 participants. Results from univariate analyses indicated that male sex (OR=2.76 95%CI [1.72; 4.43]), severe or very severe acne scarring (OR=4.28 95%CI [1.24; 14.79]), acne duration over 1 year (OR=1.71 95%CI [1.12; 2.60]), oily skin (OR=2.02 95%CI [1.27; 3.22]) and the presence of acne on the neck (OR=2.26 95%CI [1.30; 3.92]), were all significantly associated with the presence of acne scarring. Male sex (2.56 95%CI [1.58;4.17]), oily skin (1.96 95%CI [1.20;3.20]) and severe or very severe acne (3.75 95%CI [1.05;13.37]) remained significant risk factors for acne scarring in the multivariate analysis.

Conclusion

By identifying acne scarring risk factors and applying the tool in everyday dermatology visits, we can reduce the physical and psychological burden that acne scarring causes in the adolescent and adult population. Further research should be performed to reassess potential risk factors and complete the adaptation of the tool for the Ecuadorian population, with a larger and more representative study population.
COVID-19 Infection Is Associated with Poor Outcomes in Patients with Intracerebral Hemorrhage
Authors: Renedo Daniela , Leasure Audrey C. , Young Rebecca , Rivier Cyprien , Alhanti Brooke , Mac Grory Brian , Messe Steven R. , Reeves Matthew , Hassan Ameer E. , Schwamm Lee , De Havenon Adam , Matouk Charles C. , Sheth Kevin N. , Falcone Guido J.
Published: May 2023

Background

Patients with ischemic stroke and concomitant coronavirus 2019 (COVID-19) infection have worse outcomes than those without this infection. However, research on the impact of COVID-19 infection on outcomes following hemorrhagic stroke remains limited. We aim to study whether concomitant COVID-19 infection leads to worse outcomes in spontaneous intracerebral hemorrhage (ICH).

Design

We conducted an observational study using data from Get With The Guidelines® Stroke, an ongoing, multi-center, nationwide quality assurance registry.

Methods

We implemented a two-stage design: first, we compared outcomes of ICH patients with and without COVID-19 infection admitted during the pandemic (from March 2020 to February 2021). Second, we compared the same outcomes between ICH patients admitted before (March 2019 to February 2020) and during (March 2020 and February 2021) the pandemic. Main outcomes were poor functional outcome (defined as a modified Rankin Scale of 4 to 6 [mRS] at discharge), mortality and discharge to skilled nursing facility (SNF) or hospice.

Results

The first stage included 60,091 COVID-19-negative and 1,326 COVID-19-positive ICH patients. In multivariable analyses, ICH patients with versus without COVID-19 infection had 68% higher odds of poor outcome (OR 1.68, 95%CI 1.41-2.01), 51% higher odds of mortality (OR 1.51, CI 1.33-1.71) and 66% higher odds of being discharged to a SNF/hospice (OR 1.66, 95%CI 1.43-1.93). The second stage included 62,743 pre-pandemic and 64,681 intra-pandemic ICH cases. In multivariable analyses, ICH patients admitted during versus before the COVID-19 pandemic had a 10% higher odds of poor outcome (OR 1.10, 95%CI 1.07-1.14), 5% higher mortality (OR 1.05, 95%CI 1.02-1.08) and no significant difference in the risk of being discharged to SNF/hospice (OR 0.93, 95%CI 0.90-0.95).

Conclusions

The pathophysiology of the COVID-19 infection and changes in healthcare delivery during the pandemic played a role in worsening outcomes in this patient population. Further research is needed to identify these factors and understand their effect on the long-term outcome.
Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends
Authors: McCormick Lauren A , Cleary Joseph M , Hancock William O , Rice Luke M
Published: May 2023

GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which the bound nucleotide regulates the strength of tubulin:tubulin interactions is debated. The ‘self-acting’ (cis) model posits that the nucleotide (GTP or GDP) bound to a particular tubulin dictates how strongly that tubulin interacts, whereas the ‘interface-acting’ (trans) model posits that the nucleotide at the interface of two tubulin dimers is the determinant. We identified a testable difference between these mechanisms using mixed nucleotide simulations of microtubule elongation: with self-acting nucleotide, plus- and minus-end growth rates decreased in the same proportion to the amount of GDP-tubulin, whereas with interface-acting nucleotide, plus-end growth rates decreased disproportionately. We then experimentally measured plus- and minus-end elongation rates in mixed nucleotides and observed a disproportionate effect of GDP-tubulin on plus-end growth rates. Simulations of microtubule growth were consistent with GDP-tubulin binding at and ‘poisoning’ plus-ends but not at minus-ends. Quantitative agreement between simulations and experiments required nucleotide exchange at terminal plus-end subunits to mitigate the poisoning effect of GDP-tubulin there. Our results indicate that the interfacial nucleotide determines tubulin:tubulin interaction strength, thereby settling a longstanding debate over the effect of nucleotide state on microtubule dynamics.
Excitable dynamics of flares and relapses in autoimmune diseases
Authors: Lebel Yael , Milo Tomer , Bar Alon , Mayo Avi , Alon Uri
Published: May 2023

Many autoimmune diseases show flares in which symptoms erupt and then decline. A prominent example is multiple sclerosis (MS) in its relapsing-remitting phase. Mathematical models attempting to capture the flares in multiple sclerosis have often been oscillatory in nature, assuming a regular pattern of symptom flare-ups and remissions. However, this fails to account for the non-periodic nature of flares, which can appear at seemingly random intervals. Here we propose that flares resemble excitable dynamics triggered by stochastic events and show that a minimal mathematical model of autoimmune cells and inhibitory regulatory cells can provide such excitability. In our model, autoimmune response releases antigens that cause autoimmune cells to expand in a positive feedback loop, while regulatory cells inhibit the autoimmune cells in a negative feedback loop. The model can quantitatively explain the decline of MS relapses during pregnancy and their postpartum surge based on lymphocyte dynamics, as well as the decline in MS relapses with age. The model also points to potential therapeutic targets and predicts that even small modulation of regulatory T cell production, removal or activity can have a large effect on relapse rate. Excitable dynamics may underlie flares and relapses found across autoimmune diseases, thus providing an understanding that may help improve treatment strategies.
Computational insights into the conformational transition of STING: mechanistic, energetic considerations, and the influence of crucial mutations
Authors: Li Zhenlu , Yue Congran , Xie Shangqiang , Shi Sai , Ye Sheng
Published: May 2023

STING (stimulator of interferon genes) is a crucial protein in the innate immune system’s response to viral and bacterial infections. In this study, we investigated the mechanistic and energetic mechanism of the conformational transition process of STING activated by cGAMP binding. We found that the STING connector region undergoes an energetically unfavorable transition during this process, which is compensated by the favorable interaction between cGAMP and the STING ligand binding domain. We utilized enhanced sampling methods to study STING’s rotation and finds that several disease-causing mutations, such as N154S and V155L, can result in a smoother transition process, while V147L exhibits unfavorable conformational transition energy. These findings indicate that V147L may not be a gain-of-function mutation, as previously thought, and are further supported by an evolutionary analysis of the STING connector region. Overall, our study provides detailed insights into the mechanism of STING’s rotation and has implications for the development of treatments for STING-related diseases.
Spatio-temporal patterns of ovarian development andVgRgene silencing reduced fecundity of parthenogeneticArtemia
Authors: Duan Hu , Shao Xuanxuan , Liu Wei , Xiang Jianhai , Pan Namin , Wang Xuehui , Du Guoru , Li Ying , Zhou Jiaping , Sui Liying
Published: May 2023

Halophilic zooplankton brine shrimpArtemiahas been used as an experimental animal in multidisciplinary research. However, the reproductive patterns and regulation mechanisms ofArtemiaremain a mystery. In this study, the ovarian development process of parthenogeneticArtemia(P.Artemia) was distinguished into five stages, and oogenesis or egg formation process was identified with six phases. The mode of oogenesis was assumed polytrophic. Moreover, we traced the dynamic translocation of germline stem cells (GSCs) by EdU labeling, elucidated several key cytological events in oogenesis through HE staining and florescent image. Notably, distinguished from the ovary structure of insects and crustaceans, P.Artemiagermarium originated from ovariole buds and located in the base of the ovarioles. RNA-seq based on five stages of ovarian development revealed that 2657 up-regulated genes related to reproduction were obtained by pair-to-pair comparison of RNA-seq. Furthermore,Gbb, Dpp, piwi, vasa, nanos, VgAandVgRassociated with GSCs recognition and reproductive development genes were screened and also verified by qPCR. Silencing of theVgRgene in P.Artemia(PA-VgR) at stage L of ovarian development led to a low level of gene expression (<10%) within five days, which resulted variations of oogenesis-related gene expression and significantly inhibited vitellogenesis, impeded oocyte maturation, and eventually decreased the offspring number. In conclusion, we illustrated the patterns of ovarian development, outlined the key spatio-temporal features of oogenesis and established a platform for gene function research using P.Artemiaas an experimental animal. These results lay the foundation for studying the reproductive biology of invertebrates, may also provide a novel insight in the reproductive regulation mechanism of aquatic animals in extreme environments.

SUMMARY STATEMENT

Artemia is a novel experimental platform and potential “model” crustacean for studying specific process and mechanism of reproduction.
DRUM-PD/HD: The Impact of a Pilot Group Drum-Based Music Therapy Intervention on Quality of Life and Motor Symptoms in Parkinson Disease and Huntington Disease
Authors: Wainwright Lavinia , Kang Kyurim , Dayanim Gabriel , Bedell Chris , Devlin Kerry , Lanham Diane , Suarez-Cedeno Gerson , Baker Jason Armstrong , Bastepe-Gray Serap , Bang Jee , Pantelyat Alexander
Published: May 2023

Rhythm-based therapeutic interventions have widely been used in patients with neurologic disorders to address motor and quality of life outcomes. Although group drumming has been explored in several pilot studies of patients with Parkinson disease (PD) and Huntington disease (HD), caregiver burden and their quality-of-life outcomes have received less attention. Therefore, we aimed to evaluate the impact of group drumming on quality of life and motor symptoms in PD and HD patients as well as their caregivers. A total of 17 participants (PD = 6, caregivers of PD = 6, HD = 3, caregivers of HD = 2) attended the 60-minute drum-based group music therapy intervention twice a week for 12 weeks. Participants were assigned to two drumming intervention groups based on their diagnosis:1) patients diagnosed with PD and their study partners, 2) patients diagnosed with HD and their study partners. In group drumming sessions, both patients and caregiver participants utilized a variety of percussion instruments based on their personal preferences or physical abilities to facilitate movement skills and group cohesion. They were asked to complete questionnaires about quality of life and motor functioning at baseline, 6 weeks, 12 weeks, and 18 weeks (6 weeks post-intervention completion). Caregivers burden scores were also collected at these time points. Furthermore, all participants completed simple exit interview questionnaires in their follow-up visit. The PD participants and their caregivers showed an opposite trend in social role satisfaction. From baseline to 6 weeks, there were significant differences in social role satisfaction between PD participants and PD caregivers where PD participants reported a decrease in social satisfaction (Mean= -2.30,Standard Deviation= 1.64) while PD caregivers experienced an increase (M= 3.80,SD= 3.08),p= .02. In contrast, a different pattern was shown from 12 weeks to 18 weeks, where PD participants showed an increase in social satisfaction (M= 2.53,SD= 1.29), while PD caregivers demonstrated a decrease in social satisfaction (M= -2.10,SD= 3.35),p=.03. Drumming in a group setting may serve as an effective tool to enhance movement and promote social cohesion through rhythmic auditory-motor entrainment, thereby supporting quality of life in PD; further studies in HD are indicated as well.
THE IMPACT OF THE COVID-19 PANDEMIC ON NON-COVID-19 COMMUNITY-ACQUIRED PNEUMONIA, A RETROSPECTIVE COHORT STUDY
Authors: Lee Terry , Walley Keith R. , Boyd John H. , Cawcutt Kelly A. , Kalil Andre C. , Russell James A.
Published: May 2023

BACKGROUND

The COVID-19 pandemic could impact frequency and mortality of non-COVID-19 community-acquired pneumonia (CAP). Changes in frequency, patient mix, treatment, and organ dysfunction could cascade together to increase mortality of CAP during compared to pre-COVID-19.

METHODS

Hospitalized CAP patients at St. Paul’s Hospital, Vancouver, Canada pre- (fiscal years 2018/2019 and 2019/2020) and during COVID-19 pandemic (2020/2021 and 2021/2022) were evaluated.

RESULTS

In 5219 CAP patients, there was no significant difference pre-versus during pandemic in mean age, gender and Charlson co-morbidity score. However, hospital mortality increased significantly from pre-versus during COVID-19 (7.5% versus 12.1% respectively, [95% CI for difference: 3.0-6.3%], p<0.001), a 61% relative increase, coincident with increases in ICU admission (18.3% versus 25.5% respectively, [95% CI for difference: 5.0-9.5%] p<0.001, 39% relative increase) and ventilation (12.7% versus 17.5%, respectively, [95% CI for difference: 2.8-6.7%] p<0.001, 38% relative increase). Results remained the same after regression adjustment for confounders. CAP hospital admissions decreased 27% from pre- (n=1349 and 1433, 2018/2019 and 2019/2020 respectively) versus the first COVID-19 pandemic year (n=1047 in 2020/2021) then rose to pre-pandemic number (n=1390 in 2021/2022). During pre-pandemic years, CAP admissions peaked in winter; during COVID-19, the CAP admissions peaked every six months.

CONCLUSIONS AND RELEVANCE

The COVID-19 pandemic was associated with increases in hospital mortality, ICU admission and invasive mechanical ventilation rates of non-COVID-19 CAP and a transient, one year frequency decrease. There was no winter seasonality of CAP during the COVID-19 pandemic era. Future pandemic planning for CAP hospital care is needed.

What is already known on this topic

The COVID-19 pandemic could impact frequency and mortality of non-COVID-19 community-acquired pneumonia (CAP). No prior study has examined this hypothesis.

What this study adds

The COVID-19 pandemic was associated with increases in hospital mortality, ICU admission and invasive mechanical ventilation rates of non-COVID-19 CAP and a transient, one year frequency decrease. There was no winter seasonality of CAP during the COVID-19 pandemic era.

How this study might affect research, practice or policy

Future pandemic planning for CAP hospital care is needed.