bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroconvulsive Therapy: Mechanisms of Action, Clinical Considerations, and Future Directions
Authors: Kritzer Michael D. , Peterchev Angel V. , Camprodon Joan A.
Published: May 2023

Learning objectives:

• Outline and discuss the fundamental physiologic, cellular, and molecular mechanisms of ECT to devise strategies to optimize therapeutic outcomes

• Summarize the overview of ECT, its efficacy in treating depression, the known effects on cognition, evidence of mechanisms, and future directions.

Electroconvulsive therapy (ECT) is the most effective treatment for a variety of psychiatric illnesses, including treatment-resistant depression, bipolar depression, mania, catatonia, and clozapine-resistant schizophrenia. ECT is a medical and psychiatric procedure whereby electrical current is delivered to the brain under general anesthesia to induce a generalized seizure. ECT has evolved a great deal since the 1930s. Though it has been optimized for safety and to reduce adverse effects on cognition, issues persist. There is a need to understand fundamental physiologic, cellular, and molecular mechanisms of ECT to devise strategies to optimize therapeutic outcomes. Clinical trials that set out to adjust parameters, electrode placement, adjunctive medications, and patient selection are critical steps towards the goal of improving outcomes with ECT. This narrative review provides an overview of ECT, its efficacy in treating depression, its known effects on cognition, evidence of its mechanisms, and future directions.
Intraoperative Optical Coherence Tomography for Ab Interno Trabecular Bypass Glaucoma Surgery
Authors: Ang Bryan C.H. , Betzler Bjorn K. , Lim Sheng Yang
Published: May 2023

The purpose of this study was to demonstrate a case of a novel surgical technique utilizing intraoperative optical coherence tomography (iOCT) to aid implantation and optimal placement of 2 trabecular bypass minimally invasive glaucoma surgery devices—the iStent inject W and the Hydrus microstent. In iStent inject W implantation, where the depth of stent implantation has been correlated to postoperative outcomes. the iOCT allowed real-time appreciation of device implantation depth relative to the trabecular meshwork surface. In Hydrus microstent implantation, the iOCT allowed confirmation of successful stent placement within the Schlemm canal, and may help in cases where intraoperative gonioscopic view of the 3 microstent windows is impeded. This case demonstrated the use of the iOCT as an imaging adjunct to ensure optimal placement of trabecular bypass minimally invasive glaucoma surgery devices such as the iStent inject W and Hydrus microstent.
Is Kawasaki Disease Caused by a Respiratory Virus?
Authors: Rand Kenneth H. , Bhaduri-McIntosh Sumita , Gurka Matthew J. , Chi Xiaofei , Harris Alyssa
Published: May 2023

Background:

Kawasaki disease is characterized by high fever, rash, cervical lymphadenopathy, conjunctival injection, oral mucous membrane changes and swelling of the extremities followed by skin sloughing. Despite >50 years of study, no bacterial, viral or other infectious agent has been consistently associated with the illness. The lockdown and social distancing for COVID-19 in March 2020 led to a marked decrease in respiratory virus circulation. This provided an “experiment of nature” to determine whether Kawasaki disease would decline in parallel.

Methods:

Discharge ICD-10 diagnosis codes were obtained from the Vizient Clinical Data Base for Kawasaki disease and respiratory viruses, and analyzed for the age group < 5 years. Weekly respiratory virus positivity data were also obtained from BioFire Diagnostics.

Results:

Common enveloped respiratory viruses declined precipitously from April 2020 through March 2021 to levels at or below historical seasonal minimum levels. Kawasaki Disease declined about 40% compared with 2018–2019, which is distinctly different from the pattern seen for the enveloped respiratory viruses. Strong seasonality was seen for Kawasaki disease as far back as 2010, and correlated most closely with respiratory syncytial virus, human metapneumovirus and less so with influenza virus suggesting there is a baseline level of Kawasaki disease activity that is heightened during yearly respiratory virus activity but that remains at a certain level even in the near total absence of respiratory viruses.

Conclusions:

The striking decrease in enveloped respiratory viruses after lockdown and social distancing was not paralleled by a comparable decrease in Kawasaki disease incidence, suggesting a different epidemiology.
Prevalence and global trends of polypharmacy in patients with chronic liver disease: A systematic review and meta-analysis
Authors: Danjuma Mohammed Ibn-Mas’ud , Naseralallah Lina , Ansari Soubiya , Al Shebly Rafal , Elhams Mohammed , AlShamari Manwa , Kordi Ahmad , Fituri Nuha , AlMohammed Ahmed
Published: May 2023

Background:

Despite its central role in drug metabolism, the exact prevalence estimates and factors affecting global trends of polypharmacy in patients with chronic liver disease (CLD) have remained unexamined. The aim of this systematic review and meta-analysis is to estimate the prevalence of polypharmacy in patients with CLD and to comprehensively synthesize the socio-demographic factors that drive this.

Methods:

We conducted a comprehensive search of relevant databases (PubMed, EMBASE, Science citation index, Cochrane Database of Systematic Reviews, and database of abstracts of reviews of effectiveness) for studies published from inception to May 30, 2022 that reported on prevalence estimates of polypharmacy in patients with CLD. The risk of bias was conducted utilizing Loney criteria. The primary outcome was the pooled prevalence of polypharmacy in patients with CLD. We subsequently performed a systematic review and weighted meta-analysis to ascertain the exact pooled prevalence of polypharmacy among patients with CLD.

Results:

We identified approximately 50 studies from the initial literature search, of which 7 (enrolling N = 521,435 patients) with CLD met the inclusion criteria; of these, 58.7% were male, with a mean age of 53.9 (SD ± 12.2) years. The overall pooled prevalence of polypharmacy among patients with CLD was 31% (95% confidence interval [CI]: 4%–66%, I
2 = 100%, τ2 ≤ 0.001, P ≤ .0001). We found higher pooled prevalence estimates among patients aged 50 years and older compared to their younger cohorts (42%, [CI 10–77]; I2
 = 100%, P = <.001 vs 21%, [CI 0–70]; I2
 = 100%, P = <.001).

Conclusion:

In an examination of multiple community- and hospital-based databases of patients with CLD, we found a pooled prevalence estimate of polypharmacy of approximately 31%. This represents a case burden within the range reported in the general population and will likely respond to mitigation strategies employed thus far for patients in that population.
Analysis of potential biomarkers and immune infiltration in autism based on bioinformatics analysis
Authors: Cao Wenjun , Luo Chenghan , Fan Zhaohan , Lei Mengyuan , Cheng Xinru , Shi Zanyang , Mao Fengxia , Xu Qianya , Fu Zhaoqin , Zhang Qian
Published: May 2023

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder caused by both environmental and genetic factors. However, its etiology and pathogenesis remain unclear. The purpose of this study was to establish an immune-related diagnostic model for ASD using bioinformatics methods and to identify ASD biomarkers. Two ASD datasets, GSE18123 and GSE29691, were integrated into the gene expression Database to eliminate batch effects. 41 differentially expressed genes were identified by microarray data linear model (limma package). Based on the results of the immune infiltration analysis, we speculated that neutrophils, B cells naive, CD8+ T cells, and Tregs are potential core immune cells in ASD and participate in the occurrence of ASD. Finally, the differential genes and immune infiltration in ASD and non-ASD patients were compared, and the most relevant genes were selected to construct the first immune correlation prediction model of ASD. After the calculation, the model exhibited better accuracy. The calculations show that the model has good accuracy.
The effect of pre-fracture proximal femur geometry on hip fracture type in elderly patients
Authors: Çukurlu Mustafa , Karagoz Bekir , Keceli Ozan
Published: May 2023

This study aimed to analyze the relationship between fracture type by determining data on the geometry of the proximal femur in the pre-fracture period in patients over 65 years of age who had hip fractures as a result of low-energy trauma. A total of 127 patients who were admitted to the hospital for reasons other than hip pathology within 1 year before the occurrence of hip fracture and who had an anterior-posterior pelvic X-ray were included in the study. Measurements were made to evaluate the proximal femur geometry, neck shaft angle, central edge angle, femoral head diameter, femoral neck diameter, femoral neck length, femoral offset length, femoral neck axial length, hip axis length, and femoral shaft diameter. As a result of these measurements, analyses were performed to determine the relationship between the control group and fracture types. The mean Neck shaft angle scores were significantly higher in both fracture types than in the control group (P = .034, P = .002). The mean Femoral offset length values of both fracture types were lower than those of the control group (P = .002, P = .011, respectively). Multiple logistic regression analysis revealed that the risk of collum femoris fracture increased as the Femoral head diameter value increased. (OD = 0.21, P = .002). The geometric parameters of the proximal femur play an important role in the formation of hip fracture types. Therefore, differences in proximal femur geometry in hip fracture types should be considered, and patient-focused choices should be made regarding the surgical procedures and implants to be used during fracture fixation.
Correlation between lymphoma and second primary malignant tumor
Authors: Liu Lingjuan , Zhang Qun , Chen Baoan
Published: May 2023

Although studies have investigated the risk of second primary malignancies (SPMs) associated with lymphoma of various sites, limited studies have investigated risk of lymphoma with different SPMs and risk factors related to different SPMs. We conducted a retrospective cohort study to evaluate the cumulative incidence and risk factors of different secondary SPMs in patients previously diagnosed as lymphoma, and to compare the survival rates of SPMs and primary malignant tumors. Retrospective analysis was performed on data obtained from Surveillance, Epidemiology, and End Results database. Patients with an initial primary malignancy diagnosis of lymphoma between 2000 and 2019 were included in the study. The statistical analysis was conducted from March 2022 to January 2023. The development of an SPM defined as any type of malignant tumor 292,210 patients remained in final cohort, including 35,220 patients with secondary primary malignant tumor. The cumulative incidence of SPMs during 20 years of follow-up is 1.95% in combined respiratory system, 0.14% in central nervous system, is 0.82% hepatobiliary pancreatic system, is 1.31% in urinary system, is 1.92% digestive tract. Multivariate competitive risk model analysis showed that Different characteristics of lymphoma patients were associated with secondary different types of SPMS. The risk of secondary SPMs in lymphoma patients after radiotherapy and chemotherapy varies with the change of diagnosis time, diagnosis age and incubation period. Propensity score matching and Kaplan–Meier analysis showed that the survival rate of secondary tumor was significantly lower than that of matched primary malignant tumor. This study reminds us to consider the possibility of SPMs in the initial treatment of lymphoma patients, and develop a follow-up plan according to the characteristics of patients to reduce the risk of SPMs. Occurring more than 6 months after the diagnosis of lymphoma. The cumulative incidence of SPMs was estimated by Fine-Gray competing risk regression. Poisson regression was used to evaluate the therapeutic factors associated risk for SPMs in patients undergoing radiotherapy or chemotherapy. The Kaplan–Meier method was used to assess the survival outcomes of patients with SPMs.
Anxiety and depression in patients with inactive inflammatory bowel disease: The role of fatigue and health-related quality of life
Authors: Stroie Tudor , Preda Carmen , Istratescu Doina , Ciora Cosmin , Croitoru Adina , Diculescu Mircea
Published: May 2023

Inflammatory bowel diseases (IBD) are chronic conditions characterized by a remitting-relapsing course. Patients with IBD have an impaired quality of life and are more often affected by anxiety and depression. This study aimed to evaluate the prevalence and severity of anxiety and depression in patients with inactive IBD, and to identify factors associated with them. A total of 132 consecutive patients diagnosed with IBD for over 3 months that were in corticosteroid-free remission at the time of assessment were enrolled in this observational, cross-sectional study. Anxiety, depression, fatigue, and health-related quality of life (HR-QoL) were evaluated using the following self-administered questionnaires: HADS, Functional Assessment of Chronic Illness Therapy—Fatigue, and IBDQ 32. Symptoms of anxiety and depression were considered for HADS-A > 7 points and HADS-D > 7 points, respectively. Out of the 132 patients included, 76 (57.6%) were men. The median patient age was 38 years (interquartile range 30–47). Eighty-three patients (62.9%) were diagnosed with Crohn disease, and 49 (37.1%) with ulcerative colitis. Most of the patients were treated with biologics (85.6%). Anxiety was identified in 34.1% of patients, and two thirds of them (68.9%) had mild symptoms. A lower proportion of patients were presenting symptoms of depression (18.2%), the vast majority (91.7%) having mild forms. In the multivariate analysis, anxiety was significantly associated with fatigue [odds ratio (OR) 4.39, 95% confidence interval (CI): 1.22–15.79, P = .02] and lower HR-QoL (OR 2.46, 95% CI: 1.70–3.91, P < .001), while depression was associated with exposure to multiple biologics (OR 3.33, 95% CI: 1.01–10.97, P = .04) and fatigue (OR 9.70, 95% CI: 1.67–56.27, P = .01). In conclusion, anxiety and depression are highly prevalent in patients with IBD even during the periods of remission. Both anxiety and depression are associated with fatigue. In addition, lower HR-QoL is associated with anxiety and exposure to multiple biologics with depression.
Diagnostic finding on high-resolution computed tomography (HRCT) predicts a good response to pirfenidone in patients with idiopathic pulmonary fibrosis
Authors: Ma Miao , Cao Min , Gao Yujuan , Qiu Xiaohua , Jiang Hanyi , Cai Hourong
Published: May 2023

Idiopathic pulmonary fibrosis (IPF) is a debilitating condition, with a life expectancy of 2 to 5 years after diagnosis. Pirfenidone is a drug that has been shown to reduce the decline in forced vital capacity (FVC). We sought to identify whether different patterns on high-resolution computed tomography (HRCT) have different clinical effects through a retrospective comparison of baseline values and changes in pulmonary function tests (PFTs) after treatment with pirfenidone. We retrospectively analyzed data from IPF patients treated with pirfenidone at Nanjing Drum Tower Hospital in Jiangsu Province, China. According to the HRCT pattern, the patients were divided into usual interstitial pneumonitis (UIP) and possible UIP groups. Baseline clinical characteristics and changes every 6 months in the PFTs during the follow-up period were compared between the 2 groups. A total of 65 consecutive patients were enrolled. According to the HRCT pattern, patients were clustered into the UIP group (n = 46) and possible UIP group (n = 19). No difference was observed in the baseline PFTs ratio between the 2 groups. The FVC values of the 2 groups were not significantly different at the initial treatment and at 6 and 12 months after pirfenidone treatment (P = .081, 0.099, and 0.236, respectively). The improvement in % diffusion capacity of the lung for carbon monoxide (%DLCO) was higher in the possible UIP group after 6 and 12 months of pirfenidone treatment (P = .149, 0.026, and 0.025, respectively). The annual decrease in FVC was not significantly different between the 2 groups, and the annual decrease in %DLCO in the UIP group was significantly higher than that in patients with the possible UIP type (−7.767 ± 12.797 vs 0.342 ± 20.358, P < .05). These results indicate that patients with IPF with a possible UIP pattern on HRCT showed indications of a good response to pirfenidone.
When should patients take simethicone orally before colonoscopy for avoiding bubbles: A single-blind, randomized controlled study
Authors: Jung Woohyuk , Oh Gyu Man , Kim Jae Hyun , Choi Youn Jung , Son Min Young , Jung Kyoungwon , Kim Sung Eun , Moon Won , Park Moo In , Park Seun Ja
Published: May 2023

Background:

Many studies have reported the use of simethicone before colonoscopy removes bubbles. However, guidelines weakly recommend simethicone administration before colonoscopy. The present study aimed to confirm the advantages of taking simethicone and determine the appropriate time for taking simethicone.

Methods:

We randomly assigned patients to the following 5 groups according to the administration time: 4 groups were divided based on 2 parameters (the day before and on the day of colonoscopy and before and after bowel cleansing) and the remaining group was the control group. We compared bubble score (BS), number of simethicone solution irrigations when visually obscured, satisfaction score of the endoscopist, insertion time.

Results:

A total of 204 patients were included in the study. There was a difference in BS according to the timing of simethicone administration (P < .001). The group taking simethicone on the day of the test had a better BS than the group taking simethicone the day before (P < .001). The group taking simethicone on the previous day had a better BS than the control group (P = .001). In the group of taking simethicone on the examination day, the number of irrigations was lower, and satisfaction with the inspector was higher than group of taking simethicone on previous day and control group (both P < .001). The insertion time showed a non-significantly decreasing trend (P = .417).

Conclusion:

Administering simethicone reduced bubbles and facilitated effective colonoscopy, especially when administrating it on the day of examination. It needs to be administered on the day of the examination regardless of bowel preparation.
Fatal hepatic failure following atorvastatin treatment: A case report
Authors: Wang Huajun , Liu Shiyi , Zhou Chenjie , Fu Ye
Published: May 2023

Rationale:

Atorvastatin is a commonly used statin for the treatment of hypercholesterolemia in people at high risk for coronary, cerebrovascular, and peripheral artery disease. However, fatal liver failure due to atorvastatin treatment has been rarely reported, especially during the very short incubation period.

Patient concerns:

A 63-year-old male patient was admitted due to unexplained chest pain. After admission, his liver function had decreased < 24 hours after taking 20 mg tablets of atorvastatin due to lacunar infarction, which was improved after drug withdrawal. The treatment regimen was restarted 15 days later, but within 16 hours, the patient developed multiple organ failure, including liver failure and renal failure.

Diagnoses:

The pathological results after 7 days indicated focal inflammatory necrosis, virus and autoimmune correlation tests were negative, which did not rule out drug-induced liver injury. Interventions: receiving artificial liver therapy, continuous renal replacement therapy and other organ support treatment.

Outcomes:

The patient died 18 days after admission.

Lessons:

Statin idiosyncratic liver injury is very rare, but the consequences can be serious.
A case series of acute ischemic strokes with contralateral perfusion time delay on brain computed tomography
Authors: Lee Ji Min , Shin Yu Jeong , Byoung-Soo Shin , Kang Hyun Goo
Published: May 2023

Introduction:

Collateral circulation sustains cerebral perfusion in patients with arterial occlusion. Extensive arterial occlusion may redirect cerebral blood flow to compensate for insufficient perfusion. Cerebral artery occlusion can be observed in computed tomography perfusion imaging with increased mean transit time (MTT). However, in some cases, MTT delay occurs contralateral to the site of stenosis or occlusion. This delay cannot be explained simply by the collateral blood supply. Therefore, the authors considered the similarity of the perfusion delay observed at the normal site to that observed in subclavian steal syndrome.

Case presentation:

Three patients were reviewed: the first had severe stenosis in the left proximal internal carotid artery (ICA), and the second had left common carotid artery occlusion and diffusion restriction of the ICA-middle carotid artery border zone. The third patient had total occlusion of the left common carotid artery and right proximal ICA, with multifocal infarctions in the right frontal, occipital, left frontal, and parietal lobes. All 3 patients had a contralateral MTT delay on perfusion imaging.

Conclusion:

The site of stenosis or occlusion did not correlate with ipsilateral perfusion delay in these 3 cases. Based on the precedent relationship between infarction and perfusion delay, we developed 2 hypotheses to explain why perfusion decreases on the contralateral side of the occlusion or stenosis. However, this study was limited because we could not identify events, like volume loss or decreased blood pressure, before stroke development.
Update on Overactive Bladder Therapeutic Options
Authors: Babin Caroline P. , Catalano Nicole T. , Yancey David M. , Pearl Nathan Z. , Koonce Eleanor M. , Ahmadzadeh Shahab , Shekoohi Sahar , Cornett Elyse M. , Kaye Alan D.
Published: May 2023

Background:

Millions of Americans are burdened by overactive bladder (OAB) syndrome and the psychogenic and economic hardships that accompany it. Several theories attempt to explain OAB as a neurogenic dysfunction, myogenic dysfunction, urothelial dysfunction, or decreased expression of a channel protein secondary to bladder outlet obstruction. Given that the etiology of OAB is a working theory, the management of OAB is also an evolving subject matter in medicine. There are uncertainties surrounding the pathophysiology of OAB, the strength of a clinical diagnosis, and accurate reporting because of the disease's stigma and decreased use of health care.

Data Sources:

This is a narrative review that used PubMed, Google Scholar, Medline, and ScienceDirect to review literature on current and future OAB therapies.

Results:

Currently, first-line treatment for OAB is behavioral therapy that uses lifestyle modifications, bladder-control techniques, and psychotherapy. Second-line therapy includes antimuscarinic agents or beta 3 adrenergic agonists, and studies have shown that combination therapy with antimuscarinics and beta 3 adrenergic agonists provides even greater efficacy than monotherapy. Third-line therapies discussed include onabotulinumtoxinA, posterior tibial nerve stimulation, and sacral neuromodulation. OnabotulinumtoxinA has been FDA-approved as a nonpharmaceutical treatment option for refractory OAB with minimal side effects restricted to the urinary tract. Posterior tibial nerve modulation and sacral neuromodulation are successful in treating refractory OAB, but the costs and complication rates make them high-risk procedures. Therefore, surgical intervention should be a last resort. Estrogen therapy is effective in alleviating urinary incontinence in postmenopausal women, consistent with the association between estrogen deficiency and genitourinary syndrome. Potassium channel activators, voltage-gated calcium channel blockers, and phosphodiesterase inhibitors look to be promising options for the future of OAB management. As new therapies are developed, individuals with OAB can better personalize their treatment to maximize their quality of life and cost-effective care.
Pain Neuroscience Education in Elementary and Middle Schools
Authors: Louw Adriaan , Louw Colleen , Podalak Jessie , Zimney Kory , DeLorenzo Jen , Maiers Nicholas , Puentedura Emilio J. , Mintken Paul
Published: May 2023

Purpose:

The purpose of this study was to deliver pain neuroscience education (PNE) to participants in grades 3 to 8 to determine whether participants in these grades had positive shifts in pain knowledge and beliefs.

Methods:

Three hundred twenty participants, grades 3 to 8, received a 1-time, 30-minute PNE lecture. The Neurophysiology of Pain Questionnaire and the Health Care Provider's Pain and Impairment Relationship Scale were administered before and after the PNE lecture.

Results:

All grades improved in pain knowledge and beliefs. Higher-grade school participants (sixth to eighth grades) experienced larger shifts in pain knowledge and attitudes and beliefs than lower-grade (third to fifth grades) participants.

Conclusion:

PNE results in changes in pain knowledge and beliefs in school participants in grades 3 to 8.
Value of the Prognostic Nutritional Index in Surgery for Crohn Disease in China and the Effects on Outcome: A Retrospective Study
Authors: Duan Wenbiao , Qian Jiao , Chen Wenzhong , Tong Kehui , Zhang Mingyuan
Published: May 2023

Purpose:

To investigate the value of the Prognostic Nutritional Index (PNI) in the surgery of Crohn Disease and examine the ability of PNI to predict poor outcomes with surgery.

Methods:

One hundred fifty-seven patients were divided into a good nutrition group (PNI ≥40) and a poor nutrition group (PNI <40). The retrospective univariate analysis, logistic regression multivariate analysis, and receiver operating characteristic (ROC) curve analysis were used to screen out independent risk factors for postoperative complications and postoperative recurrences that required reoperation.

Results:

Penetrating behavior was an independent risk factor for postoperative complications. Emergency surgery, penetrating behavior, hypoalbuminemia, and low PNI were independent risk factors for reoperation. By the receiver operating characteristic analysis, low PNI was superior to hypoproteinemia in predicting postsurgical recurrence.

Conclusions:

PNI is a good marker for predicting surgical recurrence, but it cannot predict postoperative complications. The nutritional status in patients before elective surgery can be modified to improve PNI. It can reduce surgical recurrence to a minimum level.
Interplay of the microbiome and antifungal therapy in recurrent vulvovaginal candidiasis (RVVC): A narrative review
Authors: Bradfield Strydom Moira , Khan Sohil , Walpola Ramesh L. , Ware Robert S. , Tiralongo Evelin
Published: May 2023

Recurrent vulvovaginal candidiasis (RVVC) is a microbial, immune and sexual health disorder impacting up to 10 % of the adult female population. Fluconazole is a well-established antifungal drug commonly utilized for acute and long-term RVVC treatment. This insight review provides an overview of known vaginal and gastrointestinal microbiota characteristics in RVVC, presents the potential impacts of fluconazole therapy on multi-microbiome relationships and discusses implications for future research and clinical practice. Next-generation sequencing (NGS) and molecular methods to accurately define vaginal microbiota trends in RVVC are not comprehensively available, limiting understanding of microbiota roles in RVVC. Inconsistencies and variances in

Lactobacillus

profiles in RVVC women suggest poorly understood disease implications on the bacterial and fungal microbiomes. Investigations of environmental conditions like vaginal pH, drug therapy’s impact, especially fluconazole maintenance therapy, and the elucidation of multi-microbiome relationships in RVVC are required to further investigate disease pathogenesis and responsible antimicrobial prescribing.
Genomic analysis of 1710 surveillance-based Neisseria gonorrhoeae isolates from the USA in 2019 identifies predominant strain types and chromosomal antimicrobial-resistance determinants
Authors: Reimche Jennifer L. , Clemons Arvon A. , Chivukula Vasanta L. , Joseph Sandeep J. , Schmerer Matthew W. , Pham Cau D. , Schlanger Karen , St Cyr Sancta B. , Kersh Ellen N. , Gernert Kim M. ,   †Antimicrobial- Resistant  Working Group
Published: May 2023

This study characterized high-quality whole-genome sequences of a sentinel, surveillance-based collection of 1710

Neisseria gonorrhoeae

(GC) isolates from 2019 collected in the USA as part of the Gonococcal Isolate Surveillance Project (GISP). It aims to provide a detailed report of strain diversity, phylogenetic relationships and resistance determinant profiles associated with reduced susceptibilities to antibiotics of concern. The 1710 isolates represented 164 multilocus sequence types and 21 predominant phylogenetic clades. Common genomic determinants defined most strains’ phenotypic, reduced susceptibility to current and historic antibiotics (e.g. bla
TEM plasmid for penicillin, tetM plasmid for tetracycline, gyrA for ciprofloxacin, 23S rRNA and/or mosaic mtr operon for azithromycin, and mosaic penA for cefixime and ceftriaxone). The most predominant phylogenetic clade accounted for 21 % of the isolates, included a majority of the isolates with low-level elevated MICs to azithromycin (2.0 µg ml−1), carried a mosaic mtr operon and variants in PorB, and showed expansion with respect to data previously reported from 2018. The second largest clade predominantly carried the GyrA S91F variant, was largely ciprofloxacin resistant (MIC ≥1.0 µg ml−1), and showed significant expansion with respect to 2018. Overall, a low proportion of isolates had medium- to high-level elevated MIC to azithromycin ((≥4.0 µg ml−1), based on C2611T or A2059G 23S rRNA variants). One isolate carried the penA 60.001 allele resulting in elevated MICs to cefixime and ceftriaxone of 1.0 µg ml−1. This high-resolution snapshot of genetic profiles of 1710 GC sequences, through a comparison with 2018 data (1479 GC sequences) within the sentinel system, highlights change in proportions and expansion of select GC strains and the associated genetic mechanisms of resistance. The knowledge gained through molecular surveillance may support rapid identification of outbreaks of concern. Continued monitoring may inform public health responses to limit the development and spread of antibiotic-resistant gonorrhoea.
Morphological limitations imposed on lizards facing urbanization
Authors: Row Kristopher W. , Villasana-Espinosa Oscar , Perez Jaele , Urbina Grace , Frishkoff Luke O.
Published: May 2023

Habitat conversion in general, and urbanization in particular, are thought to create ecological filters that eliminate some species while simultaneously replacing them with others that thrive under novel conditions. The specific nature of these filters is unclear, but morphology may play an important role. Here, we seek to assess which lizard morphologies are favored in urban habitats. We quantified 17 linear measurements of morphology from museum specimens from 37 lizard species from across the continental United States. We then correlate these morphological measurements with the relative incidence of observations in urban versus non-urban environments from the citizen science database iNaturalist to determine whether particular morphologies predispose species to tolerate urban environments. We then use functional diversity and morphospace volume metrics to quantify both the total amount of unique morphological diversity represented by urban associated species, versus those restricted to natural areas. Based on our results morphology appears to be filtering lizard species from urban environments. Specifically, species with intermediate body sizes and relative tails lengths, as well as larger heads and shorter hind-limbs were more likely to occupy urban zones. As a result of this filtering, there was substantially diminished morphological diversity among urban tolerant species. While natural restricted species had a high amount of morphological diversity that was unrepresented in urban tolerant species, most urban species’ morphologies were shared by natural restricted ones. Only a small subset of morphologies found in natural environments persist in urban ones, but urban lizards do possess a small number of unique morphological features that may facilitate their success. Strong selection pressures in evolutionarily novel environments are not only diminishing species diversity but pruning phenotypic diversity to favor a much smaller subset of functional possibilities. Due to the connection between phenotype and function, such diminished morphological diversity is likely to impact ecosystem functioning in impoverished human-modified systems.
Sinogram Domain Angular Upsampling of Sparse-View Micro-CT with Dense Residual Hierarchical Transformer and Noise-Aware Loss
Authors: Adishesha Amogh Subbakrishna , Vanselow Daniel J , La Riviere Patrick , Cheng Keith C , Huang Sharon X
Published: May 2023

Reduced angular sampling is a key strategy for increasing scanning efficiency of micron-scale computed tomography (micro-CT). Despite boosting throughput, this strategy introduces noise and artifacts due to undersampling. In this work, we present a solution to this issue, by proposing a novel Dense Residual Hierarchical Transformer (DRHT) network to recover high-quality sinograms from 2 ×, 4× and 8× undersampled scans. DRHT is trained to utilize limited information available from sparsely angular sampled scans and once trained, it can be applied to recover higher-resolution sinograms from shorter scan sessions. Our proposed DRHT model aggregates the benefits of a hierarchical-multi-scale structure along with the combination of local and global feature extraction through dense residual convolutional blocks and non-overlapping window transformer blocks respectively. We also propose a novel noise-aware loss function namedKL-L1to improve sinogram restoration to full resolution. KL-L1, a weighted combination of pixel-level and distribution-level cost functions, leverages inconsistencies in noise distribution and uses learnable spatial weights to improve the training of the DRHT model. We present ablation studies and evaluations of our method against other state-of-the-art (SOTA) models over multiple datasets. Our proposed DRHT network achieves an average increase in peak signal to noise ratio (PSNR) of 17.73dB and a structural similarity index (SSIM) of 0.161, for 8× upsampling, across the three unique datasets, compared to their respective Bicubic interpolated versions. This novel approach can be utilized to decrease radiation exposure to patients and reduce imaging time for large-scale CT imaging projects.
Microscopic fractional anisotropy asymmetry in unilateral temporal lobe epilepsy
Authors: Arezza Nico J. J. , Abbas Hana , Chadwick Caroline , Johnsrude Ingrid S. , Burneo Jorge , Khan Ali R. , Baron Corey A.
Published: May 2023

Objectives

Surgical resection is the method of choice for treating medically refractory unilateral temporal lobe epilepsy (TLE), but postsurgical prognosis depends on magnetic resonance imaging (MRI) findings. Seizure freedom is more often achieved after resection in MRI-positive patients (those with MRI abnormalities such as mesial temporal sclerosis) than in MRI-negative patients. Diffusion MRI shows promise as a marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. However, fractional anisotropy is not specific to axon integrity in grey matter where axon orientation is not uniform. In contrast, microscopic fractional anisotropy is a recently introduced dMRI technique that is sensitive to axon integrity regardless of axon orientation. This work investigated whether microscopic fractional anisotropy may be sensitive to hippocampal abnormalities in unilateral TLE.

Methods

Diffusion MRI was performed on a 3T scanner in 9 patients (age = 33 +/- 12 years) with unilateral TLE and 9 healthy volunteers (age = 26 +/- 6). A deep learning method was employed to segment the hippocampus into smaller subfields corresponding to the subiculum, cornu ammonis (CA) 1, CA2/3, and CA4 plus dentate gyrus (DG). Mean ipsilateral and contralateral measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared to investigate asymmetry in each subfield.

Results

Microscopic fractional anisotropy was reduced, and diffusivity was elevated in the ipsilateral CA4/DG region relative to the contralateral side in all 9 patients. Asymmetries in diffusion metrics between the left and right sides of the hippocampus subfields were not observed in the healthy volunteers.

Significance

Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its insensitivity to axon orientation, microscopic fractional anisotropy may yield a more robust measurement than fractional anisotropy and may improve epileptic focus localization in surgical candidates.
Factors associated with the near miss of pregnant and postpartum women hospitalized by Covid-19
Authors: da Silva Ana Carolina Schultz , Moroskoski Márcia , de Oliveira Natan Nascimento , de Brito Franciele Aline Machado , de Andrade Pereira Silva Marcela , Salci Maria Aparecida , Carreira Lígia , Nickenig Vissoci João Ricardo , de Oliveira Rosana Rosseto
Published: May 2023

Objective

To analyze the factors associated with maternal near miss due to Covid-19 in Brazil.

Method

cross-sectional study that assessed the cases of pregnant and postpartum women hospitalized with SARS due to Covid-19, aged between 10 and 49 years and from March 2020 to March 2022. Secondary data available in the Influenza Epidemiological Surveillance Information System (SIVEP-Flu) were used. Data were analyzed using SPSS statistical software, with univariate analysis followed by logistic regression.

Results

the significant independent factors associated with near miss in pregnant postpartum women due to Covid-19 were black/brown race, O2 saturation <95%, dyspnea, comorbidities, need for invasive and non-invasive ventilatory support.

Conclusion

the factors associated with near misses in pregnant and postpartum women with covid-19 reveal characteristics and risks inherent to the pathophysiology of the disease that contribute to worsening the condition.
Defining a core configuration for human centromeres during mitosis
Authors: Gupta Ayantika Sen , Seidel Chris , Tsuchiya Dai , McKinney Sean , Yu Zulin , Smith Sarah , Unruh Jay , Gerton Jennifer L.
Published: May 2023

The biorientation of sister chromatids on the mitotic spindle, essential for accurate sister chromatid segregation, relies on critical centromere components including cohesin, the centromere-specific H3 variant CENP-A, and centromeric DNA. Centromeric DNA is highly variable between chromosomes yet must accomplish a similar function. Moreover, how the 50 nm cohesin ring, proposed to encircle sister chromatids, accommodates inter-sister centromeric distances of hundreds of nanometers on the metaphase spindle is a conundrum. Insight into the 3D organization of centromere components would help resolve how centromeres function on the mitotic spindle. We used ChIP-seq and super-resolution microscopy to examine the geometry of essential centromeric components on human chromosomes. ChIP-seq demonstrates that cohesin subunits are depleted in α-satellite arrays where CENP-A nucleosomes and kinetochores assemble. Cohesin is instead enriched at pericentromeric DNA. Structured illumination microscopy of sister centromeres is consistent, revealing a non-overlapping pattern of CENP-A and cohesin. We used single particle averaging of hundreds of mitotic sister chromatids to develop an average centromere model. CENP-A clusters on sister chromatids, connected by α-satellite, are separated by ∼562 nm with a perpendicular intervening ∼190 nM wide axis of cohesin. Two differently sized α-satellite arrays on chromosome 7 display similar inter-sister CENP-A cluster distance, demonstrating different sized arrays can achieve a common spacing. Our data suggest a working model for a common core configuration of essential centromeric components that includes CENP-A nucleosomes at the outer edge of extensible α-satellite DNA and pericentromeric cohesion. This configuration helps reconcile how centromeres function and serves as a foundation for future studies of additional components required for centromere function.
Design to Data for mutants of B-glucosidase B fromPaenibacillus polymyxa: V311D, F248N, Y166H, Y166K, M221K
Authors: Chan Morgan , Siegel Justin B. , Vater Ashley
Published: May 2023

Engaging computational tools for protein design is gaining traction in the enzyme engineering community. However, current design and modeling algorithms have limited functionality predictive capacities for enzymes due to limitations of the dataset in terms of size and data quality. This study aims to expand training datasets for improved algorithm development with the addition of five rationally designed single-point enzyme variants. β-glucosidase B variants were modeled in Foldit Standalone and then produced and assayed for thermal stability and kinetic parameters. Functional parameters: thermal stability (TM) and Michaelis-Menten constants (kcat, KM, andkcat/KM) of five variants, V311D, Y166H, M221K, F248N, and Y166K, were added into the Design2Data database. As a case study, evaluation of this small mutant set finds mutational effect trends that both corroborate and contradict findings from larger studies examining the entire dataset.
Effect of Mangiferin Isolated fromHedysarum neglectumL. Root Culture on Fat Accumulation in ExperimentsIn Vivo
Authors: Fedorova Anastasia M. , Prosekov Alexander Y. , Milentyeva Irina S. , Minina Varvara I. , Ostapova Elena V.
Published: May 2023

Plant polyphenols possess diverse medicinal and therapeutic properties. For instance, they can prevent such age-related diseases as stroke, heart attack, type II diabetes, and their various pathological complications. Mangiferin is a polyphenolic compound with a C-glycosylxanthone structure. This biologically active substance is known for its antioxidant, anti-inflammatory, antimicrobial, antidiabetic, and immunomodulatory properties. This research features mangiferin isolated fromHedysarum neglectumL. root culture and its effect on fat accumulation inCaenorhabditis elegansN2 Bristol. A set of experimentsin vivoproved that mangiferin was able to inhibit fat accumulation in the model organism. The optimal concentration was determined as 50 μm: it provided 44.5% fluorescence.
Mild/Asymptomatic Maternal SARS-CoV-2 Infection Leads to Immune Paralysis in Fetal Circulation and Immune Dysregulation in Fetal-Placental Tissues
Authors: Doratt Brianna M. , Sureshchandra Suhas , True Heather , Rincon Monica , Marshall Nicole , Messaoudi Ilhem
Published: May 2023

Few studies have addressed the impact of maternal mild/asymptomatic SARS-CoV-2 infection on the developing neonatal immune system. In this study, we analyzed umbilical cord blood and placental chorionic villi from newborns of unvaccinated mothers with mild/asymptomatic SARS-CoV-2 infection during pregnancy using flow cytometry, single-cell transcriptomics, and functional assays. Despite the lack of vertical transmission, levels of inflammatory mediators were altered in cord blood. Maternal infection was also associated with increased memory T, B cells, and non-classical monocytes as well as increased activation. However,ex vivoresponses to stimulation were attenuated. Finally, within the placental villi, we report an expansion of fetal Hofbauer cells and infiltrating maternal macrophages and rewiring towards a heightened inflammatory state. In contrast to cord blood monocytes, placental myeloid cells were primed for heightened antiviral responses. Taken together, this study highlights dysregulated fetal immune cell responses in response to mild maternal SARS-CoV-2 infection during pregnancy.
Oryza CLIMtools: A Genome-Environment Association Resource Reveals Adaptive Roles for Heterotrimeric G Proteins in the Regulation of Rice Agronomic Traits
Authors: Ferrero-Serrano Ángel , Chakravorty David , Kirven Kobie J. , Assmann Sarah M.
Published: May 2023

Modern crop varieties display a degree of mismatch between their current distributions and the suitability of the local climate for their productivity. To this end, we present Oryza CLIMtools (https://gramene.org/CLIMtools/oryza_v1.0/), the first resource for pan-genome prediction of climate-associated genetic variants in a crop species. Oryza CLIMtools consists of interactive web-based databases that allow the user to: i) explore the local environments of traditional rice varieties (landraces) in South-Eastern Asia, and; ii) investigate the environment by genome associations for 658 Indica and 283 Japonica rice landrace accessions collected from georeferenced local environments and included in the 3K Rice Genomes Project. We exemplify the value of these resources, identifying an interplay between flowering time and temperature in the local environment that is facilitated by adaptive natural variation inOsHD2and disrupted by a natural variant inOsSOC1. Prior QTL analysis has suggested the importance of heterotrimeric G proteins in the control of agronomic traits. Accordingly, we analyzed the climate associations of natural variants in the different heterotrimeric G protein subunits. We identified a coordinated role of G proteins in adaptation to the prevailing Potential Evapotranspiration gradient and their regulation of key agronomic traits including plant height and seed and panicle length. We conclude by highlighting the prospect of targeting heterotrimeric G proteins to produce crops that are climate resilient.
Exposing the molecular heterogeneity of glycosylated biotherapeutics
Authors: Schachner Luis F. , Mullen Christopher , Phung Wilson , Hinkle Joshua D. , Beardsley Michelle Irwin , Bentley Tracy , Day Peter , Tsai Christina , Sukumaran Siddharth , Baginski Tomasz , DiCara Danielle , Agard Nicholas , Masureel Matthieu , Gober Joshua , ElSohly Adel , Syka John E. P. , Huguet Romain , Marty Michael T. , Sandoval Wendy
Published: May 2023

Glycosylated biotherapeutics are an emerging class of drugs with high molecular heterogeneity, which can affect their safety and efficacy. Characterizing this heterogeneity is crucial for drug development and quality assessment, but existing methods are limited in their ability to analyze intact glycoproteins. Here, we present a new approach to glycoform fingerprinting that uses proton-transfer charge-reduction with gas-phase fractionation to analyze intact glycoproteins by mass spectrometry. The method provides a detailed landscape of the intact molecular weights present in biotherapeutic protein preparations in a single experiment and offers insights into glycoform composition when coupled with a suitable bioinformatic strategy. We tested the approach on various biotherapeutic molecules, including Fc-fusion, VHH-fusion, and peptide-bound MHC class II complexes to demonstrate efficacy in measuring the proteoform-level diversity of biotherapeutics. Notably, we inferred the glycoform distribution for hundreds of molecular weights for the eight-times glycosylated fusion drug IL22-Fc, enabling correlations between glycoform sub-populations and the drug’s pharmacological properties. Our method is broadly applicable and provides a powerful tool to assess the molecular heterogeneity of emerging biotherapeutics.