bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Ocular Higher-Order Aberrations in First-Degree Relatives of Patients With Keratoconus
Authors: Namdari Maral , Eslampour Alireza , Zarei-Ghanavati Siamak
Published: May 2022

Purpose:

The aim of this study was to evaluate the corneal higher-order aberrations (HOAs) in first-degree relatives of patients with keratoconus (KCN) and compare with the normal population.

Methods:

In this prospective comparative study, 210 eyes from 105 family members of 28 patients with KCN and 210 normal eyes of 105 controls were enrolled. In each eye, corneal topography, tomography, and aberrometry were performed and compared between the 2 groups.

Results:

This study included 61 female (58.1%) and 44 male participants (41.9%) and 105 age-matched and sex-matched controls with normal topographic cornea. In 14 of 105 first-degree relatives (13.33%) of patients with KCN, KCN was diagnosed with a male preponderance (71.5% male, 28.5% female). Tomographic indices and irregularity indices in 3 and 5 mm zone in Orbscan were significantly higher in the relative group. In addition, other irregularity indices of TMS-4 topography including surface regularity index, surface asymmetry index, difference sector index, SDP, and irregular astigmatism index were significantly higher in family members of patients with KCN. The most prevalent topographic pattern in the control group was the symmetric bowtie (57.1%) and in the relative group was the asymmetric bowtie (39.5%). In addition, significantly thinnest corneal pachymetry was detected in the relative group. Root mean square of all HOAs including vertical trefoil, vertical coma, horizontal coma, horizontal trefoil, quadrifoil, and fourth-order spherical aberrations were significantly greater in the relative group than controls.

Conclusions:

Owing to the high prevalence of undiagnosed KCN susceptibility in family members with KCN, keratorefractive surgery should be considered cautiously in these individuals. In addition, comprehensive preoperative examination should be considered to detect subtle topographic and HOAs in these individuals.
Altered serum bile acid profile in fibromyalgia is associated with specific gut microbiome changes and symptom severity
Authors: Minerbi Amir , Gonzalez Emmanuel , Brereton Nicholas , Fitzcharles Mary-Ann , Chevalier Stéphanie , Shir Yoram
Published: May 2022

Alterations in the composition and function of the gut microbiome in women with fibromyalgia have recently been demonstrated, including changes in the relative abundance of certain bile acid–metabolizing bacteria. Bile acids can affect multiple physiological processes, including visceral pain, but have yet to be explored for association to the fibromyalgia gut microbiome. In this study, 16S rRNA sequencing and targeted metabolomic approaches were used to characterize the gut microbiome and circulating bile acids in a cohort of 42 women with fibromyalgia and 42 healthy controls. Alterations in the relative abundance of several bacterial species known to metabolize bile acids were observed in women with fibromyalgia, accompanied by significant alterations in the serum concentration of secondary bile acids, including a marked depletion of α-muricholic acid. Statistical learning algorithms could accurately detect individuals with fibromyalgia using the concentration of these serum bile acids. Serum α-muricholic acid was highly correlated with symptom severity, including pain intensity and fatigue. Taken together, these findings suggest serum bile acid alterations are implicated in nociplastic pain. The changes observed in the composition of the gut microbiota and the concentration of circulating secondary bile acids seem congruent with the phenotype of increased nociception and are quantitatively correlated with symptom severity. This is a first demonstration of circulating bile acid alteration in individuals with fibromyalgia, potentially secondary to upstream gut microbiome alterations. If corroborated in independent studies, these observations may allow for the development of molecular diagnostic aids for fibromyalgia as well as mechanistic insights into the syndrome.
Treatment of idiopathic overactive bladder with botulinum toxin: real-life results and patients’ expectations
Authors: Abreu-Mendes Pedro , Portugal-Rodrigues Inês , Vale Luis , Dinis Paulo , Cruz Francisco , Antunes-Lopes Tiago , Martins-Silva Carlos
Published: May 2022

Background:

Overactive bladder (OAB) is a prevalent syndrome affecting 11% to 16% of the adult population. When first-line pharmacological therapy is not effective, intradetrusorial injections of onabotulinumtoxinA (BTX-A) might have an important role in controlling symptoms. The main aim of this study was to access both the efficacy and safety of intradetrusor injections of 100U BTX-A in real clinical practice, among women with idiopathic OAB (iOAB).

Methods:

Retrospective study, based on clinical diaries in 136 iOAB female patients, with or without urinary incontinence, submitted to BTX-A injections, between 2005 and 2018 in a tertiary university hospital. Positive response was considered only when the patient mentioned she had great improvement after the injection, otherwise, it was considered negative.

Results:

A positive response was obtained in 90 patients (66%) after the first injection. Women with a positive response after the first treatment had 7.5 times more chances to improve with the second (P 
= .01). Discontinuation of the therapy after the first injection was neither dependent on the presence of incontinence at baseline (P = .73) nor it was related to age (P = .6). On univariate analyses, none of the parameters evaluated was useful of predicting successful response, although there was a trend in women who had had a previous midurethral sling surgery for stress urinary incontinence, to have a lower chance of having a positive response after the first injection (P = .06).

Thirty-nine women (29%) had at least 1 adverse event, urinary tract infection, and straining to void were the most frequent. Women above 65 years old had less risk of developing a urinary tract infection (P = .04).

Conclusion:

In real clinical practice, BTX-A injection is an effective (66%) and safe treatment, capable of improving quality of life. Moreover, responding to the first injection seems to predict good clinical outcomes in the second treatment. This procedure can be done with minimal restrictions.
Data Collection Procedures and Injury Definitions in Badminton: A Consensus Statement According to the Delphi Approach
Authors: Gijon-Nogueron Gabriel , Ortega-Avila Ana Belen , Kaldau Niels Christian , Fahlstrom Martin , Felder Hanno , Kerr Stewart , King Mark , McCaig Steve , Marchena-Rodriguez Ana , Cabello-Manrique David
Published: May 2022

Previous studies involving injury surveillance in badminton players have used nonstandardized injury definitions and data collection methodologies. The purpose of this study was to apply a Delphi method to (1) reach a consensus on an injury definition in badminton and (2) develop a standardized badminton injury report form. An Injury Consensus Group was established under the auspices of the Badminton World Federation, and initial injury definitions and injury report form were developed. An internal panel was formed from the Injury Consensus Group, and an external panel was selected based on a combination of profession, experience in the field, sport-specific knowledge/expertise, and geographical location to obtain a widely representative sample. Through 2 rounds of voting by the external panel, consensus was reached on both the definition of an injury in badminton and a standardized injury report form. The agreed injury definition was “Any physical injury sustained by a player during a match or training regardless if further diagnostic tests were done or if playing time was lost” and the injury report form contained the following 7 sections: Injury record, Diagnosis, Injury mechanism, Regarding pain, Pain and return to play/training after injury, Grade of severity, and Recurrence. We recommend the use of the definitions and methods presented in this consensus statement for the reporting of injury in all international and domestic badminton players. This should make future injury surveillance reports directly comparable and hence more informative in recognizing trends over time and differences between countries.
Finding Predictors of Azathioprine-Induced Pancreatitis in Patients With Inflammatory Bowel Disease
Authors: Freitas Marta , Lima Capela Tiago , Macedo Silva Vítor , Arieira Cátia , Cúrdia Gonçalves Tiago , Dias de Castro Francisca , Moreira Maria João , Firmino-Machado João , Cotter José
Published: May 2022

Objectives

Azathioprine (AZA)-induced pancreatitis (AIP) is a common, idiosyncratic adverse effect whose incidence and risk factors data in inflammatory bowel disease (IBD) patients are not fully clarified. We aimed to establish the incidence, clinical course and identify risk factors for AIP.

Methods

A retrospective study including all IBD patients on AZA between January 2013 and July 2020 was conducted. Patients with AIP were considered.

Results

Azathioprine-induced pancreatitis occurred in 33 patients (7.5%; 442 patients on AZA). The mean time receiving AZA until AIP was 25 days, with a mean dose of 88 mg. All patients had a mild course of disease, which resolved with suspension of AZA and with no complications. Smoking (P = 0.02), single daily dose of AZA (P < 0.001), and concomitant budesonide (P = 0.001) were risk factors for AIP. In multivariate analysis, concomitant treatment with budesonide (odds ratio, 5.3; P = 0.002) and single daily dose of AZA (odds ratio, 3.8; P = 0.002) were the only predictors of AIP.

Conclusions

Although AIP was a relatively common adverse effect, it presented a mild course in all patients. Smoking, concomitant use of budesonide, and single-dose regimen of AZA should be avoided in IBD patients treated with AZA.
Baseline Factors Predictive of the Receipt of Second-Line Chemotherapy After Nab-Paclitaxel Plus Gemcitabine for Patients With Advanced Pancreatic Cancer
Authors: Iede Kiyotsugu , Yamada Terumasa , Koh Masahiro , Ueda Masami , Tsuda Yujiro , Nakashima Shinsuke , Ohta Katsuya , Tanida Tsukasa , Matsuyama Jin , Ikenaga Masakazu , Tominaga Shusei
Published: May 2022

Objective

Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC.

Methods

Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated.

Results

Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity.

Conclusions

Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.
Pancreatic Neuroendocrine Tumors
Authors: Lee Sara , Maegawa Felipe B. , Joseph Sharon , Alvarado Luis A. , Mendoza-Ladd Antonio , Elhanafi Sherif , Philipovskiy Alexander , Tyroch Alan H. , Konstantinidis Ioannis T.
Published: May 2022

Objectives

During the last decades, significant progress has been made in the management of patients with pancreatic neuroendocrine tumors (pNETs). It is unclear how the type of the treating health care facility alters patient outcomes.

Methods

Data from pNETs reported to the National Cancer Database between 2004 and 2016 were examined. Types of institutions were as follows: academic/research cancer program (ARP), comprehensive community cancer program (CCCP), integrated network cancer program (INCP), and community cancer program (CCP).

Results

A total of 17,887 patients with pNETs were analyzed. Treatment at ARPs was significantly associated with receipt of surgery (ARP, 61.9%; CCCP, 45.6%; CCP, 29.9%; INCP, 55.5%; P < 0.001), both for patients with very early tumors ≤2 cm (ARP, 74.7%; CCCP, 66.5%; CCP, 52.4%; INCP, 71.6%; P < 0.001) and for patients with liver metastases (ARP, 21.3%; CCCP, 10.6%; CCP, 5%; INCP, 16.8%; P < 0.001). Treatment at ARPs was associated with improved survival (median overall survival: ARP, 91 mo; CCCP, 47 mo; CCP, 24.5 mo; INCP, 72 mo; P < 0.001).

Conclusions

Treatment of pNETs at academic/research programs is associated with more frequent resections and best survival outcomes. This survival benefit exists for early and late stages and after adjusting for known cofactors.
Cotesting for Human Immunodeficiency Virus and Sexually Transmitted Infections in the Emergency Department
Authors: Seballos Spencer S. , Lopez Rocio , Hustey Fredric M. , Schold Jesse D. , Kadkhoda Kamran , McShane Adam J. , Phelan Michael P.
Published: May 2022

Background

The Centers for Disease Control and Prevention (CDC) and US Preventive Services Task Force (USPSTF) guidelines recommend screening for human immunodeficiency virus (HIV) in patients aged 15 to 65 years, as well as those at increased risk. Patients screened in the emergency department (ED) for gonorrhea (GC) and/or chlamydia represent an increased-risk population. Our aim was to assess compliance with CDC and USPSTF guidelines for HIV testing in a national sample of EDs.

Methods

We examined data from the 2010 to 2018 Nationwide Emergency Department Sample, which can be used to create national estimates of ED care to query tests for GC, chlamydia, HIV, and syphilis testing. Weighted proportions and 95% confidence intervals (CIs) were reported, and Rao-Scott χ2 tests were used.

Results

We identified 13,443,831 (weighted n = 3,094,214) high-risk encounters in which GC/chlamydia testing was performed. HIV screening was performed in 3.9% (95% CI, 3.4–4.3) of such visits, and syphilis testing was performed in 2.9% (95% CI, 2.7–3.2). Only 1.5% of patients with increased risk encounters received both HIV and syphilis cotesting.

Conclusions

Despite CDC and USPSTF recommendations for HIV and syphilis screening in patients undergoing STI evaluation, only a small proportion of patients are being tested. Further studies exploring the barriers to HIV screening in patients undergoing STI assessment in the ED may help inform future projects aimed at increasing guidance compliance.
Nodular Liver in Portosinusoidal Vascular Disease: A Case of Mistaken Identity
Authors: Alkashash Ahmad M. , Khan Shahbaz , Nephew Lauren , Kubal Chandrashekhar A. , Nelson Nick , Saxena Romil
Published: May 2022

Background

Portosinusoidal vascular disease (PSVD) has been proposed as a unifying term for vascular abnormalities of the small portal veins and sinusoids that occur in the noncirrhotic liver. This term supersedes other designations including incomplete septal cirrhosis, nodular regenerative hyperplasia, hepatoportal sclerosis, and obliterative portal venopathy. Most patients have noncirrhotic portal hypertension, but the latter is not required to establish a diagnosis of PSVD. Diagnosis requires a liver biopsy of adequate size (≥20 mm long) in the presence of accompanying clinical signs of noncirrhotic portal hypertension and/or histological changes of PSVD. We report a case of severe PSVD that caused severe liver atrophy and required transplantation for intractable hepatic encephalopathy. The explanted liver showed numerous focal nodular hyperplasia-like nodules.

Case Report

A 57-year-old man with neurofibromatosis type 2 and diabetes mellitus type 2 controlled with insulin developed ascites and signs of portal hypertension. He was presumed to have cirrhosis due to nonalcoholic fatty liver disease and underwent liver transplantation for intractable portal hypertension and severe hepatic encephalopathy. The explanted liver had a nodular appearance; however, histological sections showed no bridging fibrosis. Thin, incomplete curvilinear fibrous septa were seen emanating from portal tracts in a patchy distribution. Our case illustrates that PSVD may cause severe hepatic atrophy and lead to architectural abnormalities that may radiologically mimic the parenchymal nodularity of cirrhosis.
Synchronous Mucinous Carcinomas of Ovary and Appendix: A Case Report With Diagnostic Pitfalls and Review of Corresponding Literature
Authors: Hegazy Shaymaa , Bhargava Rohit , Roy Somak , Elishaev Esther
Published: May 2022

Background

Diagnosis of the primary ovarian mucinous neoplasms occasionally poses a challenge because historically most tumors diagnosed as primary ovarian were documented as metastases from gastrointestinal and pancreatobiliary tracts. This challenge is attributed to the overlapping histologic features, the gray zone, between primary and metastatic mucinous neoplasms in the ovary. While presentation of both primary and metastatic mucinous tumors manifests by the presence of an ovarian mass, determination of the site of origin is clinically significant, because most treatment guidelines are based on the tissue of origin.

Case Presentation

We present an unusual case of mucinous adenocarcinoma of the ovary and the appendix with diagnostic pitfalls and challenges of immunohistochemical profile.

Conclusion

Utilization of molecular analysis in challenging cases of ovarian neoplasms helps to narrow down the gray zone and lessens the misdiagnosis of primary ovarian mucinous tumors.
Sarcomatoid Mesothelioma With Bland Histologic Features: A Potential Pitfall in Diagnosis
Authors: Burke Allen , Hardy Naomi , Fanaroff Rachel , Legesse Teklu
Published: May 2022

Sarcomatoid mesotheliomas can be challenging to diagnose on small biopsy specimens, where limited material may preclude definitive assessment of invasion, and lesional cells can have relatively bland cytology with no mesothelial marker expression. We report a case of a patient who presented with a pleural effusion and had subsequent pleural biopsy that showed a bland, uniform spindle cell proliferation in a mildly myxoid background. There was little, if any, collagen and no chest wall, soft tissue, or fat, and mesothelial markers were negative. The cells were positive for pancytokeratin and GATA3 by immunohistochemistry, and in situ hybridization showed a “negative” result for homozygous loss of CDKN2A; however, there was partial (heterozygous) loss of 1 allele. A diagnosis of atypical spindle cell proliferation was made based on these findings. Several months later, the patient had a repeat pleural biopsy that showed spindled cells with more pleomorphism, areas of invasion into the chest wall, and the same partial loss of CDKN2A, consistent with a sarcomatoid mesothelioma. This case underscores the challenges present on small biopsy specimens and the fact that sarcomatoid mesotheliomas can be relatively bland-appearing with focal pleomorphism and that heterozygous loss of CDKN2A should be considered a positive result indicative of a neoplastic process.
Impact of Opioid Restriction Legislation on Prescribing Practices for Outpatient Plastic and Reconstructive Surgery
Authors: O’Brien Andrew L. , Krasniak Peter J. , Schroeder Michael J. , Desai Miraj N. , Diaz Adrian , Chetta Matthew D.
Published: May 2022

Background:

Overprescription of opioids for acute postoperative pain, plastic surgery procedures included, is contributing to the pervasive opioid epidemic in the United States. This study examines the effect of a statewide legislation limiting postoperative opioids on opioid prescription behavior among providers following outpatient plastic surgery procedures at a high-volume academic center.

Methods:

Retrospective review of all outpatient surgical encounters between June 1, 2016, and November 30, 2018, was performed. Encounters were grouped into two cohorts: prepolicy and postpolicy. Primary outcomes included total oral morphine equivalents prescribed on the day of surgery and proportion of patients prescribed greater than 210 oral morphine equivalents. Secondary outcomes included proportion of patients requiring an opioid refill within 30 days following surgery, and number of refills required.

Results:

The mean oral morphine equivalents prescribed on the day of surgery was reduced from 271.8 to 150.37 oral morphine equivalents (p < 0.001) following implementation of the legislation, with an associated decrease in the standard deviation of oral morphine equivalents prescribed from 225.35 to 196.71 (p < 0.001), suggesting a decrease in the variability of prescriber practices. Time series analysis demonstrated the decrease in oral morphine equivalents remained significant when accounting for baseline level of change in opioid prescription patterns.

Conclusion:

This study provides evidence that legislation at the state level restricting postoperative opioid prescriptions is associated with a decrease in opioid prescriptions without an increase in the need for refills in the acute postoperative setting following outpatient plastic surgery procedures.
Quality characteristics of fermented garlic by various lactic acid
bacteria
Authors: Song Doyoung , Hwang Do-Young , Park Kyung-Hee , Park Jeom-Leon , Kang Seong-Gook , Ham Kyung-Sik
Published: May 2022

This study aimed to investigate quality characteristics and antioxidant activity
of garlic fermented by lactic acid bacteria (LAB). Four LAB strains
(Lactobacillus plantarum KCTC3108, Lactobacillus
plantarum B8, Lactobacillus plantarum BR4 and
Leuconostoc mesenteroides SY3) were selected for analysis
based on their fermentation ability (pH and total acidity) from eight LAB
strains isolated from fermented foods. Quality characteristics and antioxidant
activity were measured during four days of fermentation. S-allyl-L-cysteine,
total thiosulfinate content, total flavonoid content and ferric reducing
antioxidant power of fermented garlic extract increased as fermentation
progressed. After fermentation, the S-allyl-L-cysteine contents of garlic
samples fermented with L. plantarum KCTC3108, L.
plantarum B8, L. plantarum BR4 and
Leuconostoc mesenteroides SY3 increased 2.34, 2.30, 1.96
and 2.62 times, respectively, and the total thiosulfinate contents increased
5.55, 6.06, 14.41, and 7.56 times, respectively, compared to those at the
beginning of fermentation. Ferric reducing antioxidant power and total flavonoid
content were 23.64 mg/mL and 144.65 μg/mL, respectively
in garlic samples fermented with L. plantarum BR4 which were
the highest values among the groups. Based on these results, L.
plantarum BR4 was selected for garlic fermentation to develop a
functional food.
Quality characteristics of yakju added with lactic
acid bacteria-fermented ginseng sprouts
Authors: Kim Su-Hwan , Woo Hyo-Gyeong , Choi Yu-Ri , Lee Chae-Mi , Jeong Jae-Hee , Lee Dong-Hun , Lee Chae-Yun , Oh Im-Kyung , Ha Ho-Kyung , Kim Jung-Sil , Choi Byung-Kuk , Huh Chang-Ki
Published: May 2022

This study aimed to improve the physiological activity and processing properties
of ginseng sprouts. We first determined the effect of extraction and
fermentation conditions on the antioxidant activity of ginseng sprouts. The
optimal extraction conditions were 2 h at 80°C, with water as a solvent.
The fermentation strains used were Lactobacillus delbrueckii
subsp. bulgaricus KCTC 3635 and Enterococcus
faecalis KCTC 3206. We then analyzed the changes in the reducing
sugar and alcohol content. In fermented samples, the reducing sugar content was
lower and the alcohol content was higher than those in control sample. The cell
counts of lactic acid bacteria were higher in the fermented samples than those
in the control sample. Fermented samples contained more ginsenoside than the
extract samples, and ginsenoside was not detected in the control sample. The
total polyphenol and total flavonoid contents were relatively high in the
fermented samples, particularly in the sample fermented by E.
faecalis. Finally, sensory evaluation revealed that the
Yakju prepared using ginseng sprouts fermented by lactic
acid bacteria was preferable to other drinks control and ginseng sprouts
extracted sample. Overall, it was confirme that the addition of fermented
ginseng improved the physiological activity and palatability of
yakju, there by improving the quality of
yakju.
Risks and challenges in COVID-19 infection prevention and control in a hospital setting: perspectives of healthcare workers in Thailand
Authors: Jongdeepaisal Monnaphat , Chunekamrai Puri , Maude Rapeephan R , Maude Richard J
Published: May 2022

In hospital settings, awareness of, and responsiveness to, COVID-19 are crucial to reducing the risk of transmission among healthcare workers (HCWs) and protecting them from infection. Healthcare professionals can offer insights into the practicalities of infection prevention and control measures and on how the protective equipment and training could best be delivered during the pandemic. This study aimed to inform the development of future recommendations to optimise compliance with appropriate use of these measures, and to improve the guidance to reduce their risk of the disease. Drawing on in-depth interviews with HCWs in a hospital in Thailand, several factors influence the use of multiple prevention measures: concerns about infection, availability of the equipment supply, barriers to work performance, and physical limitations in the hospital setting. Setting a ventilated outdoor space for screening and testing, and interaction through mobile technology, were perceived to reduce the transmission risk for staff and patients. Adequate training, clear guidelines, streamlined communications, and management support are crucial to encourage appropriate use of, and adherence to, implementation of infection prevention and control (IPC) measures among HCW. Further study should explore the perceptions and experience of health professionals in local health facilities and community-based workers during the pandemic, particularly in resource-limited settings.
Seasonal movement of royal chambers: where are the kings and queens of temperate termites in winter?
Authors: Takata Mamoru , Konishi Takao , Nagai Shuya , Nozaki Tomonari , Tasaki Eisuke , Matsuura Kenji
Published: May 2022

Overwintering is a critical part of the annual cycle for species that live in temperate, polar, and alpine regions. As a result, low-temperature biology is a key determinant of temperate species distribution. Termites distribute predominantly in tropical regions, and only a few species are found in the temperate zone. As with other social insects, termites are characterized by the division of labor between reproductive and non-reproductive castes in which the survival of reproductives is crucial to maintaining their society. Here, in the termiteReticulitermes speratus, we report the discovery of an underground royal chamber that kings and queens use to survive the winter, which is separate from the one they use during the warmer breeding season. Our investigation of field colonies indicates that in the spring the royals are localized in decayed logs on the ground, then move to their underground royal chamber located in the roots of stumps in the fall. The winter minimum temperature measured in the royal chamber was higher than the ground surface temperature. In overwintering termites, the kings and queens had higher cold tolerance than workers and soldiers. The kings and queens were at risk of mortality from −8 °C, compared to the workers and soldiers at −4 °C. Air temperatures dropped below this critical temperature of −8 °C multiple times, as evidenced from the past 140 years of weather records in Kyoto. This suggests that the underground movement of the royal chamber may contribute to avoiding the risk of overwintering mortality. These results demonstrate the social strategies implemented to overcome the environment met while living at the latitudinal limits. This study sheds light on one of the most important aspects of the biology of termites in terms of predicting their geographic distribution and spread by climate change. This work also helps further the understanding of the termite’s social system, seasonal phenology, long-term survivorship, and life cycle, and contributes to the development of pest control strategies.
DrugRepo: A novel approach to repurpose a huge collection of compounds based on chemical and genomic features
Authors: Wang Yinyin , Aldahdooh Jehad , Hu Yingying , Yang Hongbin , Vähä-Koskela Markus , Tang Jing , Tanoli Ziaurrehman
Published: May 2022

The drug development process consumes 9-12 years and approximately one billion US dollars in terms of costs. Due to high finances and time costs required by the traditional drug discovery paradigm, repurposing the old drugs to treat cancer and rare diseases is becoming popular. Computational approaches are mainly data-driven and involve a systematic analysis of different data types leading to the formulation of repurposing hypotheses. This study presents a novel scoring algorithm based on chemical and genomic data types to repurpose vast collection of compounds for 674 cancer types and other diseases. The data types used to design the scoring algorithm are chemical structures, drug-target interactions (DTI), pathways, and disease-gene associations. The repurpose scoring algorithm is strengthened by integrating the most comprehensive manually curated datasets for each data type. More than 100 of our repurposed compounds can be matched with ongoing studies at clinical trials (https://clinicaltrials.gov/). Our analysis is supported by a web tool available at: http://drugrepo.org/.
Detecting intragenic trans-splicing events with hybrid transcriptome sequencing in cancer cells
Authors: Chen Yu-Chen , Chen Chia-Ying , Chiang Tai-Wei , Chan Ming-Hsien , Hsiao Michael , Ke Huei-Mien , Tsai Isheng Jason , Chuang Trees-Juen
Published: May 2022

Trans-splicing can generate non-co-linear (NCL) transcripts that consist of exons in an order topologically inconsistent with the corresponding DNA template. Detecting trans-spliced RNAs (ts-RNAs) may be interfered by false positives from experimental artifacts, circular RNAs (circRNAs), and genetic rearrangements. Particularly, intragenic ts-RNAs, which are derived from separate precursor mRNA molecules of the same genes, are often mistaken for circRNAs through analyses of high-throughput transcriptome sequencing (RNA-seq) data. In addition, the biogenesis and function of ts-RNAs remain elusive. Here we developed a bioinformatics pipeline, NCLscan-hybrid, with the integration of long and short RNA-seq reads to minimize false positives and identify intragenic ts-RNAs. We utilized two features of long reads, out-of-circle and rolling circle, to distinguish intragenic ts-RNAs from circRNAs. We also designed multiple experimental validation steps to examine each type of false positives and successfully confirmed an intragenic ts-RNA (ts-ARFGEF1) in breast cancer cells. On the basis of ectopic expression and CRISPR-based endogenous genome modification experiments, we confirmed that ts-ARFGEF1 formation was significantly dependent on the reverse complementary sequences in the flanking introns of the NCL junction. Subsequent in vitro and in vivo experiments demonstrated that ts-ARFGEF1 silencing can significantly inhibit tumor cell growth. We further showed the regulatory role of ts-ARFGEF1 in p53-mediated apoptosis through affecting the PERK/eIF2a/ATF4/CHOP signaling pathway in breast cancer cells. This study thus described both bioinformatics procedures and experimental validation steps for rigorous characterization of transcriptionally non-co-linear RNAs, expanding the discovery of this important but understudied class of RNAs.
A platform for efficient establishment, expansion and drug response profiling of high-grade serous ovarian cancer organoids
Authors: Senkowski Wojciech , Gall-Mas Laura , Falco Matias Marin , Li Yilin , Lavikka Kari , Kriegbaum Mette C. , Oikkonen Jaana , Bulanova Daria , Pietras Elin J. , Voßgröne Karolin , Chen Yan-Jun , Erkan Erdogan Pekcan , Høg Mia Kristine Grønning , Larsen Ida Marie , Lamminen Tarja , Kaipio Katja , Huvila Jutta , Virtanen Anni , Engelholm Lars , Christiansen Pernille , Santoni-Rugiu Eric , Huhtinen Kaisa , Carpén Olli , Hynninen Johanna , Hautaniemi Sampsa , Vähärautio Anna , Wennerberg Krister
Published: May 2022

The broad research use of organoids from high-grade serous ovarian carcinoma (HGSC) has been hampered by low culture success rates and limited availability of fresh tumor material. Here we describe a method for generation and long-term expansion of HGSC organoids with efficacy markedly improved over previous reports (55% vs. 23-38%). We established organoids from cryopreserved material, demonstrating the feasibility of using viably biobanked tissue for HGSC organoid derivation. Genomic, histologic and single-cell transcriptomic analyses revealed that organoids recapitulated genetic and phenotypic features of original tumors. Organoid drug responses correlated with clinical treatment outcomes, although in culture conditions-dependent manner and only in organoids maintained in human plasma-like medium (HPLM). Organoids from consenting patients are available to the research community through a public biobank and organoid genomic data explorable through an interactive online tool. Taken together, this resource facilitates the application of HGSC organoids in basic and translational ovarian cancer research.
Latent dynamics of primary sensory cortical population activity is structured by fluctuations in the local field potential
Authors: Sederberg Audrey , Pala Aurélie , Stanley Garrett B
Published: May 2022

As emerging technologies enable measurement of precise details of the activity within microcircuits at ever-increasing scales, there is a growing need to identify the salient features and patterns within the neural populations that represent physiologically and behaviorally relevant aspects of the network. Accumulating evidence from recordings of large neural populations suggests that neural population activity frequently exhibits relatively low-dimensional structure, with a small number of variables explaining a substantial fraction of the structure of the activity. While such structure has been observed across the brain, it is not known how reduced-dimension representations of neural population activity relate to classical metrics of “brain state,” typically described in terms of fluctuations in the local field potential (LFP), single-cell activity, and behavioral metrics. Here, we relate the latent dynamics of spiking activity of populations of neurons in the whisker area of primary somatosensory cortex of awake mice to classic measurements of cortical state in S1. We found that a hidden Markov model fit the population spiking data well with a relatively small number of states, and that putative inhibitory neurons played an outsize role in determining the latent state dynamics. Spiking states inferred from the model were more informative of the cortical state than a direct readout of the spiking activity of single neurons or of the population. Further, the spiking states predicted both the trial-by-trial variability in sensory responses and one aspect of behavior, whisking activity. Our results show how classical measurements of brain state relate to neural population spiking dynamics at the scale of the microcircuit and provide an approach for quantitative mapping of brain state dynamics across brain areas.

Author Summary

Brain states have long been known to strongly shape sensory perception, decision making, cognition, and movement. Brain state during wakefulness changes constantly, classically assessed using changes in the spectral features of the local field potential (LFP) and behavioral measures. However, the connection between these classical measurements of brain state and the collective dynamics of populations of neurons is unclear. Here we fit a latent-variable model to population spiking activity, finding that latent variables inferred under the model are highly predictive of cortical state changes and that the latent dynamics are profoundly shaped by inhibitory cell activity. Our approach connects the activity patterns of ensembles of neurons to a classical measurement of brain state and opens new avenues for investigating brain state dynamics across diverse cortical areas.
Modelling eNvironment for Isoforms (MoNvIso): A general platform to predict structural determinants of protein isoforms in genetic diseases
Authors: Oliva Francesco , Musiani Francesco , Giorgetti Alejandro , De Rubeis Silvia , Sorokina Oksana , Armstrong J. Douglas , Carloni Paolo , Ruggerone Paolo
Published: May 2022

The seamless integration of human disease-related mutation data into protein structures is an essential component of any attempt to correctly assess the impact of the mutation. The key step preliminary to any structural modelling is the identification of the correct isoform onto which mutations should be mapped because there are several functionally different protein isoforms from the same gene. To handle large sets of data coming from omics techniques, this challenging task should be automatized. Here we present our code MoNvIso (Modelling eNvironment for Isoforms), which pinpoints the correct isoform associated with the mutation of interest and builds a structural model of both the wild type isoform and the related variants starting from the name of the gene and the list of mutations of interest.
Differential regulation of gene expression pathways with dexamethasone and ACTH after early life seizures
Authors: Brabec Jeffrey L. , Ouardouz Mohamed , Mahoney J. Matthew , Scott Rod C. , Hernan Amanda E.
Published: May 2022

Early-life seizures (ELS) are associated with persistent cognitive deficits such as ADHD and memory impairment. These co-morbidities have a dramatic negative impact on the quality of life of patients. Therapies that improve cognitive outcomes have enormous potential to improve patients’ quality of life. Our previous work in a rat flurothyl-induction model showed that administration of adrenocorticotropic hormone (ACTH) at time of seizure induction led to improved learning and memory in the animals despite no effect on seizure latency or duration. Administration of dexamethasone (Dex), a corticosteroid, did not have the same positive effect on learning and memory and has even been shown to exacerbate injury in a rat model of temporal lobe epilepsy. We hypothesized that ACTH exerted positive effects on cognitive outcomes through beneficial changes to gene expression and proposed that administration of ACTH at seizure induction would return gene-expression in the brain towards the normal pattern of expression in the Control animals whereas Dex would not. Twenty-six Sprague-Dawley rats were randomized into vehicle- Control, and ACTH-, Dex-, and vehicle-ELS. Rat pups were subjected to 60 flurothyl seizures from P5 to P15. After seizure induction, brains were removed and the hippocampus and PFC were dissected, RNA was extracted and sequenced, and differential expression analysis was performed using generalized estimating equations. Differential expression analysis showed that ACTH pushes gene expression in the brain back to a more normal state of expression through enrichment of pathways involved in supporting homeostatic balance and down-regulating pathways that might contribute to excitotoxic cell-damage post-ELS.
Comparison of immunogenicity and safety of inactivated, adenovirus-vectored and heterologous adenovirus-vectored/mRNA vaccines in patients with systemic lupus erythematosus and rheumatoid arthritis: a prospective cohort study
Authors: Assawasaksakul Theerada , Lertussavavivat Tanat , Sathitratanacheewin Seelwan , Oudomying Nont , Vichaiwattana Preeyaporn , Wanlapakorn Nasamon , Poovorawan Yong , Avihingsanon Yingyos , Assawasaksakul Nawaporn , Kittanamongkolchai Wonngarm
Published: May 2022

Background

Impaired immune response to COVID-19 vaccines have been observed in autoimmune rheumatic disease patients. Determining the most effective and safe vaccine regimen is critically needed in such a population. We aim to compare the immunogenicity and safety of three COVID-19 vaccine regimens in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods

SLE and RA patients aged 18-65 years who received inactivated (CoronaVac or COVILO), adenovirus-vectored (AZD1222), or heterogeneous (AZD1222/BNT162b2) vaccines were enrolled. Humoral and cellular immune responses were assessed at day 28 after the second vaccination. This was performed using the serum binding antibody level against receptor-binding domain of the SARS-CoV-2 spike protein (anti-RBD Ig) and IFNy-ELISpot assay (ELISpot) respectively. Reactogenicity was reviewed on day 7 following each vaccination. Disease activity was assessed before and on day 28 after the second vaccination.

Results

The cohort consisted of 94 patients (64 SLE and 30 RA). Inactivated, AZD1222, and AZD1222/BNT162b2 vaccines were administered to 23, 43, and 28 patients, respectively. Anti-RBD titers were lowest in the inactivated vaccine group (2.84 AU/mL; 95% CI 0.96-8.44), followed by AZD1222 (233.7 AU/mL; 95% CI 99.0 - 505.5) and AZD1222/BNT162b2 (688.6 AU/mL; 95% CI 271 - 1745), p 0<0.0001. After adjusting for relevant factors, the inactivated vaccine was associated with the lowest humoral response, while adenovirus-vectored/mRNA vaccine was the highest. The proportion of positive ELISpot test was also lowest in the inactivated vaccine group (27%), followed by the adenovirus-vectored vaccine (67%), and adenovirus-vectored/mRNA vaccine (73%)(p = 0.03). All types of vaccine were well-tolerated. There was no flare of autoimmune disease post-vaccination.

Conclusion

Adenovirus-vectored and adenovirus-vectored/mRNA vaccines elicited a stronger humoral and cellular immune response than inactivated vaccines, suggesting that they may be more suitable in SLE and RA patients receiving immunosuppressive therapy.
A protein signature associated with active tuberculosis identified by plasma profiling and network-based analysis
Authors: Mousavian Zaynab , Folkesson Elin , Fröberg Gabrielle , Foroogh Fariba , Correia-Neves Margarida , Bruchfeld Judith , Källenius Gunilla , Sundling Christopher
Published: May 2022

Objectives

Tuberculosis (TB) is a bacterial infectious disease caused byMycobacterium tuberculosis. Annually, an estimated 10 million people are diagnosed with active TB, and approximately 1.4 million dies of the disease. If left untreated, each person with active TB will infect 10 to 15 new individuals every year. Therefore, interrupting disease transmission by accurate early detection and diagnosis, paired with appropriate treatment is of major importance. In this study, we aimed to identify biomarkers associated with the development of active TB that can then be further developed for clinical testing.

Methods

We assessed the relative plasma concentration of 92 proteins associated with inflammation in individuals with active TB (n=19), latent TB (n=13), or healthy controls (n=10). We then constructed weighted protein co-expression networks to reveal correlations between protein expression profiles in all samples. After clustering the networks into four modules, we assessed their association with active TB.

Results

One module consisting of 16 proteins was highly associated with active TB. We used multiple independent transcriptomic datasets from studies investigating respiratory infections and non-TB diseases. We then identified and removed genes encoding proteins within the module that were low expressed in active TB or associated with non-TB diseases, resulting in a 12-protein plasma signature associated with active TB.

Conclusion

We identified a plasma protein signature that is highly enriched in patients with active TB but not in individuals with latent TB or healthy controls and that also had minimal cross-reactivity with common viral or bacterial lower respiratory tract infections.
Advancing antimicrobial resistance monitoring in surface waters with metagenomic and quasimetagenomic methods
Authors: Ottesen Andrea , Kocurek Brandon , Ramachandran Padmini , Reed Elizabeth , Commichaux Seth , Engelbach Gunnar , Mammel Mark , Fleurant Sanchez Saint , Zhao Shaohua , Kabera Claudine , Merrill Amy , Bonin Nathalie , Worley Hannah , Noyes Noelle , Boucher Christina , McDermott Patrick , Strain Errol
Published: May 2022

Surface waters present a unique challenge for the monitoring of critically important antimicrobial resistance. Metagenomic approaches provide unbiased descriptions of taxonomy and antimicrobial resistance genes in many environments, but for surface water, culture independent data is insufficient to describe critically important resistance. To address this challenge and expand resistome reporting capacity of antimicrobial resistance in surface waters, we apply metagenomic and quasimetagenomic (enriched microbiome) data to examine and contrast water from two sites, a creek near a hospital, and a reservoir used for recreation and municipal water. Approximately 30% of the National Antimicrobial Resistance Monitoring System’s critically important resistance gene targets were identified in enriched data contrasted to only 1% in culture independent data. Four different analytical approaches consistently reported substantially more antimicrobial resistance genes in quasimetagenomic data compared to culture independent data across most classes of antimicrobial resistance. Statistically significant differential fold changes (p<0.05) of resistance determinants were used to infer microbiological differences in the waters. Important pathogens associated with critical antimicrobial resistance were described for each water source. While the single time-point for only two sites represents a small pilot project, the successful reporting of critically important resistance determinants is proof of concept that the quasimetagenomic approach is robust and can be expanded to multiple sites and timepoints for national and global monitoring and surveillance of antimicrobial resistance in surface waters.
Loss of the chromatin remodeler, ATRX, promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin receptor binding
Authors: DeWitt Suzanne Bartholf , Plumlee Sarah Hoskinson , Brighton Hailey E. , Sivaraj Dharshan , Martz E. J. , Zand Maryam , Kumar Vardhman , Sheth Maya U. , Floyd Warren , Spruance Jacob , Hawkey Nathan , Varghese Shyni , Ruan Jianhua , Kirsch David G. , Somarelli Jason A. , Alman Ben , Eward William C.
Published: May 2022

Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-κB signaling, extracellular matrix remodeling, increased integrin αvβ3 expression, and ETS family transcription factor binding. Here we characterize these changes in vitro, in vivo, and in a dataset of human OS patients. This increased aggression substantially sensitizes ATRX-deficient OS cells to integrin signaling inhibition. Thus, ATRX plays an important tumor suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between ATRX expression and integrin binding, NF-κB activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with ATRX loss, including other cancers and the ATR-X alpha thalassemia mental retardation syndrome.