bluuebunny/crossref_metadata_2025 huggingface dataset:
Case-Control Study to Estimate the Association Between Tdap Vaccination During Pregnancy and Reduced Risk of Pertussis in Newborn Infants in Peru, 2019–2021
Authors: Juscamayta-López Eduardo , Valdivia Faviola , Soto María Pía , Horna Helen , Pajuelo Mónica
Published: June 2023

Background

Despite widespread vaccination, pertussis has re-emerged as a serious public health concern worldwide. Since 2017, Peru has experienced an increase in pertussis cases exhibiting a higher risk of severity and death in young infants. Thus, a dose of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended for pregnant women in the third trimester. Although evidence suggests the maternal Tdap vaccine is safe and effective, its association with a reduced risk of pertussis in developing countries remains poorly investigated.

Methods

We conducted a case-control study to evaluate the association between Tdap vaccination during pregnancy and reduction in the risk of pertussis among infants aged <2 months in Peru. Pertussis cases and controls treated in healthcare facilities nationwide between 2019 and 2021 and confirmed by real-time polymerase chain reaction were included. The controls were randomly selected from test-negative patients. Odds ratios (ORs) and vaccine effectiveness (VE) were calculated using a multiple logistic regression model and 1 − (OR) × 100%, respectively.

Results

Fifty cases and 150 controls were included in the analysis. The mothers of 4% of cases and 16.7% of controls received Tdap vaccination during pregnancy, resulting in an OR of 0.19 (95% confidence interval [CI], .04–.86) and VE of 81% (95% CI, 14%–96%) for preventing pertussis in infants.

Conclusions

Peruvian infants <2 months old whose mothers received the Tdap vaccine in the third trimester of pregnancy had a significantly lower risk of pertussis. The Tdap vaccination is thus an effective intervention to reduce the burden of pertussis in at-risk populations.
Insights into vascular physiology from sleep photoplethysmography
Authors: Yilmaz Gizem , Ong Ju Lynn , Ling Lieng-Hsi , Chee Michael W L
Published: June 2023

Study Objectives

Photoplethysmography (PPG) in consumer sleep trackers is now widely available and used to assess heart rate variability (HRV) for sleep staging. However, PPG waveform changes during sleep can also inform about vascular elasticity in healthy persons who constitute a majority of users. To assess its potential value, we traced the evolution of PPG pulse waveform during sleep alongside measurements of HRV and blood pressure (BP).

Methods

Seventy-eight healthy adults (50% male, median [IQR range] age: 29.5 [23.0, 43.8]) underwent overnight polysomnography (PSG) with fingertip PPG, ambulatory blood pressure monitoring, and electrocardiography (ECG). Selected PPG features that reflect arterial stiffness: systolic to diastolic distance (∆T_norm), normalized rising slope (Rslope) and normalized reflection index (RI) were derived using a custom-built algorithm. Pulse arrival time (PAT) was calculated using ECG and PPG signals. The effect of sleep stage on these measures of arterial elasticity and how this pattern of sleep stage evolution differed with participant age were investigated.

Results

BP, heart rate (HR) and PAT were reduced with deeper non-REM sleep but these changes were unaffected by the age range tested. After adjusting for lowered HR, ∆T_norm, Rslope, and RI showed significant effects of sleep stage, whereby deeper sleep was associated with lower arterial stiffness. Age was significantly correlated with the amount of sleep-related change in ∆T_norm, Rslope, and RI, and remained a significant predictor of RI after adjustment for sex, body mass index, office BP, and sleep efficiency.

Conclusions

The current findings indicate that the magnitude of sleep-related change in PPG waveform can provide useful information about vascular elasticity and age effects on this in healthy adults.
Cytotoxicity screening ofThymus vulgarisL. in breast cancer: in vitro study
Authors: Bıtgen Nazmiye , Onder Gozde Ozge , Baran Munevver , Yay Arzu
Published: June 2023

Breast cancer is one of the leading causes of cancer-related deaths due to its aggressive course. There is an increasing need for alternative therapy strategies, including herbal medications, to treat the disease because of its high incidence. Medicinal plants, such as Thymus vulgaris L. (T. vulgaris), have recently attracted great interest due to the antitumor properties of their extracts. The purpose of this investigation was to ascertain whether T. vulgaris had any cytotoxic effects on two different breast cancer cell lines. MTT test was applied to evaluate the effect of T. vulgaris on cell viability. TUNEL method was used to determine its apoptotic effect. LC3 and Beclin-1 expression levels were determined by immunofluorescence staining method and its autophagic effect was evaluated. Our findings demonstrate that T. vulgaris greately lowers proliferation, both in terms of concentration and duration. Consistent with decreased proliferation, an increase in apoptotic and autophagic cell death were also observed. The migration capacity of MCF-7 and MDA-MB-231 breast cancer cells was greatly suppressed by T. vulgaris, while significantly reducing colony formation. This study is the first to look into how T. vulgaris methanol extract affects breast cancer cells. All of these findings demonstrate that T. vulgaris prevents breast cancer cells from developing a malignant phenotype. It is possible to say that the methanol extract of T. vulgaris is suitable for the treatment of breast cancer, including aggressive types. However, in vivo research should support these results.
Transmission and Management of Pathogenic Agrobacterium tumefaciens and Rhodococcus fascians in Select Ornamentals
Authors: Gordon Michael I. , Thomas William J. , Putnam Melodie L.
Published: June 2023

Pathogenic Agrobacterium tumefaciens and Rhodococcus fascians are phytobacteria that induce crown gall and leafy gall disease, respectively, resulting in undesirable growth abnormalities. When present in nurseries, plants infected by either bacterium are destroyed, resulting in substantial losses for growers, especially those producing plants valued for their ornamental attributes. There are many unanswered questions regarding pathogen transmission on tools used to take cuttings for propagation and whether products used for bacterial disease control are effective. We investigated the ability to transmit pathogenic A. tumefaciens and R. fascians on secateurs and the efficacy of registered control products against both bacteria in vitro and in vivo. Experimental plants used were Rosa × hybrida, Leucanthemum × superbum, and Chrysanthemum × grandiflorum for A. tumefaciens and Petunia × hybrida and Oenothera ‘Siskiyou’ with R. fascians. In separate experiments, we found secateurs could convey both bacteria in numbers sufficient to initiate disease in a host-dependent manner and that bacteria could be recovered from secateurs after a single cut through an infected stem. In in vivo assays, none of six products tested against A. tumefaciens prevented crown gall disease, although several products appeared promising in in vitro trials. Likewise, four compounds trialed against R. fascians failed to prevent disease. Sanitation and clean planting material remain the primary means of disease management.
Cognitive assessment in primary care
Authors: Clevenger Carolyn K. , Schlenger Alison , Gunter Debbie , Glasgow Glenna Brewster
Published: June 2023

Primary care clinicians play a critical role in both the identification and management of cognitive impairment due to common diseases. Primary care practices should incorporate feasible, reliable, and helpful tools into existing workflow to recognize and support people living with dementia and their care partners.
The Statistical Fragility of Trials Comparing Cervical Disc Arthroplasty and Anterior Cervical Discectomy and Fusion
Authors: Ortiz-Babilonia Carlos D. , Gupta Arjun , Cartagena-Reyes Miguel A. , Xu Amy L. , Raad Micheal , Durand Wesley M. , Skolasky Richard L. , Jain Amit
Published: June 2023

Study Design.

Meta-analysis

Objective.

Assess the robustness of randomized controlled trials (RCTs) that compared cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) for the treatment of symptomatic degenerative cervical pathology by using fragility indices.

Summary of Background Data.

RCTs comparing these surgical approaches have shown that CDA may be equivalent or even superior to ACDF due to better preservation of normal spinal kinematics.

Methods.

RCTs reporting clinical outcomes after CDA versus ACDF for degenerative cervical disc disease were evaluated. Data for outcome measures were classified as continuous or dichotomous. Continuous outcomes included: Neck Disability Index (NDI), overall pain, neck pain, radicular arm pain, and modified Japanese Orthopaedic Association (mJOA) scores. Dichotomous outcomes included: any adjacent segment disease (ASD), superior-level ASD, and inferior-level ASD. The fragility index (FI) and continuous FI (CFI) were determined for dichotomous and continuous outcomes, respectively. The corresponding fragility quotient (FQ) and continuous FQ (CFQ) were calculated by dividing FI/CFI by sample size.

Results.

Twenty-five studies (78 outcome events) were included. Thirteen dichotomous events had a median FI of 7 (IQR: 3–10) and the median FQ was 0.043 (IQR: 0.035–0.066). Sixty-five continuous events had a median CFI of 14 (IQR: 9–22) and median CFQ of 0.145 (IQR: 0.074–0.188). This indicates that, on average, altering the outcome of 4.3 patients out of 100 for the dichotomous outcomes, and 14.5 out of 100 for continuous outcomes, would reverse trial significance. Of the 13 dichotomous events that included lost to follow-up data, 8 (61.5%) represented ≥7 patients lost. Of the 65 continuous events reporting lost to follow-up data, 22 (33.8%) represented ≥14 patients lost.

Conclusion.

RCTs comparing ACDF and CDA have fair to moderate statistical robustness and do not suffer from statistical fragility.
Preoperative Symptom Duration Influences Neurological Recovery and Patient　Reported Outcome Measures After Surgical Treatment of Cervical Ossification of the Posterior Longitudinal Ligament
Authors: Matsukura Yu , Egawa Satoru , Inose Hiroyuki , Sakai Kenichiro , Kusano Kazuo , Tsutsui Shunji , Hirai Takashi , Matsukura Yu , Wada Kanichiro , Katsumi Keiichi , Koda Masao , Kimura Atsushi , Furuya Takeo , Maki Satoshi , Nagoshi Narihito , Nishida Norihiro , Nagamoto Yukitaka , Oshima Yasushi , Ando Kei , Nakashima Hiroaki , Takahata Masahiko , Mori Kanji , Nakajima Hideaki , Murata Kazuma , Miyagi Masayuki , Kaito Takashi , Yamada Kei , Banno Tomohiro , Kato Satoshi , Ohba Tetsuro , Moridaira Hiroshi , Fujibayashi Shunsuke , Katoh Hiroyuki , Kanno Haruo , Taneichi Hiroshi , Imagama Shiro , Kawaguchi Yoshiharu , Takeshita Katsushi , Nakamura Masaya , Matsumoto Morio , Yamazaki Masashi , Okawa Atsushi , Yoshii Toshitaka
Published: June 2023

Study Design:

A prospective multicenter study.

Objective:

To investigate the effect of preoperative symptom duration on neurological recovery for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL).

Summary of Background Data:

The optimal timing to perform surgery in the setting of cervical OPLL remains unknown. It is important to know the influence of symptom duration on postoperative outcomes to facilitate discussions regarding the timing of surgery.

Methods:

The study included 395 patients (291 men and 104 women, mean age 63.7±11.4 y): 204 treated with laminoplasty, 90 with posterior decompression and fusion, 85 with anterior decompression and fusion, and 16 with other procedures. The Japanese Orthopedic Association (JOA) score and patient reported outcomes of JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) were used to assess clinical outcomes preoperatively and two years following surgery. Logistic regression analysis was used to identify factors associated with achievement of MCID following surgery.

Results:

The recovery rate was significantly lower in the group with symptom duration of ≥5 years compared to the groups with durations of <0.5 years, 0.5–1 year, and 1-2 years. Improvement of JOACMEQ in the upper extremity function score (P<0.001), lower extremity function (P=0.039), quality of life (P=0.053) and bladder function (P=0.034) were all decreased when the symptom duration exceeded 2 years. Duration of symptoms (P=0.001), age (P<0.001), and BMI (P<0.001) were significantly associated with the achievement of MCID. The cutoff value we established for symptom duration was 23 months (AUC 0.616, sensitivity 67.4%; specificity 53.5%).

Conclusions:

Symptom duration had a significant impact on neurological recovery and patient reported outcome measures in this series of patients undergoing surgery for cervical OPLL. Patients with symptom duration exceeding 23 months may be at greater risk of failing to achieve MCID after surgery.

Level of Evidence:

3.
Does the 2017 global initiative for chronic obstructive lung disease revision really improve the assessment of Chinese chronic obstructive pulmonary disease patients? A multicenter prospective study for more than 5 years
Authors: Cui Yanan , Ma Yiming , Dai Zhongshang , Long Yingjiao , Chen Yan
Published: June 2023

Background:

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 proposed a new classification that reclassified many chronic obstructive pulmonary disease (COPD) patients from group D to B. However, there is a paucity of data related to the comparison between reclassified and non-reclassified COPD patients in terms of long-term prognosis. This study aimed to investigate long-term outcomes of them and determine whether the GOLD 2017 revision improved the assessment of COPD patients.

Methods:

This observational, multicenter, prospective study recruited outpatients at 12 tertiary hospitals in China from November 2016 to February 2018 and followed them up until February 2022. All enrolled patients were classified into groups A to D based on GOLD 2017, and the subjects in group B included patients reclassified from group D to B (group DB) and those remaining in group B (group BB). Incidence rates and hazard ratios (HRs) were calculated for the exacerbation of COPD and hospitalization in each group.

Results:

We included and followed up 845 patients. During the first year of follow-up, the GOLD 2017 classification had a better discrimination ability for different risks of COPD exacerbation and hospitalization than GOLD 2013. Group DB was associated with a higher risk of moderate-to-severe exacerbation (HR = 1.88, 95% confidence interval [CI] = 1.37–2.59, P < 0.001) and hospitalization for COPD exacerbation (HR = 2.23, 95% CI = 1.29–3.85, P = 0.004) than group BB. However, during the last year of follow-up, the differences in the risks of frequent exacerbations and hospitalizations between group DB and BB were not statistically significant (frequent exacerbations: HR = 1.02, 95% CI = 0.51–2.03, P = 0.955; frequent hospitalizations: HR = 1.66, 95% CI = 0.58–4.78, P = 0.348). The mortality rates of the two groups were both approximately 9.0% during the entire follow-up period.

Conclusions:

The long-term prognosis of patients reclassified into group B and of those remaining in group B was similar, although patients reclassified from group D to group B had worse short-term outcomes. The GOLD 2017 revision could improve the assessment of Chinese COPD patients in terms of long-term prognosis.
Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons
Authors: Kim Hyoung Woo , Shim Sang Wook , Zhao Anna Mae , Roh Dahee , Han Hye Min , Middleton Steven J. , Kim Wheedong , Chung Sena , Johnson Errin , Prentice John , Tacon Mike , Koel-Simmelink Marleen J.A. , Wieske Luuk , Teunissen Charlotte E. , Bae Yong Chul , Bennett David L.H. , Rinaldi Simon , Davies Alexander J. , Oh Seog Bae
Published: June 2023

Traumatic peripheral nerve injuries are at high risk of neuropathic pain for which novel effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance. Traumatic nerve injuries seen in the clinic commonly result in axonotmesis (ie, crush), yet the neuropathic phenotype of “painful” nerve crush injuries remains poorly understood. We report the neuropathology and sensory symptoms of a focal nerve crush injury using custom-modified hemostats resulting in either complete (“full”) or incomplete (“partial”) axonotmesis in adult mice. Assays of thermal and mechanically evoked pain-like behavior were paralleled by transmission electron microscopy, immunohistochemistry, and anatomical tracing of the peripheral nerve. In both crush models, motor function was equally affected early after injury; by contrast, partial crush of the nerve resulted in the early return of pinprick sensitivity, followed by a transient thermal and chronic tactile hypersensitivity of the affected hind paw, which was not observed after a full crush injury. The partially crushed nerve was characterized by the sparing of small-diameter myelinated axons and intraepidermal nerve fibers, fewer dorsal root ganglia expressing the injury marker activating transcription factor 3, and lower serum levels of neurofilament light chain. By day 30, axons showed signs of reduced myelin thickness. In summary, the escape of small-diameter axons from Wallerian degeneration is likely a determinant of chronic pain pathophysiology distinct from the general response to complete nerve injury.
Gross Hematuria and Lower Urinary Tract Symptoms Associated With Military Burn Pits Exposures in US Veterans Deployed to Iraq and Afghanistan
Authors: Perveen Mosammat M. , Mayo-Malasky Henry E. , Lee-Wong Mary F. , Tomaska Julie M. , Forsyth Edward , Gravely Amy , Klein Mark A. , Trembley Janeen H. , Butterick Tammy A. , Promisloff Robert A. , Ginex Pamela K. , Barach Paul , Szema Anthony M.
Published: June 2023

Objective

The aim of the study is to describe rates of hematuria and other lower urinary tract symptoms, including self-reported cancer rates, among veterans postburn pits emissions exposure during deployment to Iraq and Afghanistan.

Methods

US post-9/11 veterans with burn pits emissions exposure confirmed via DD214 forms in the Burn Pits360.org Registry were sent a modified survey. Data were deidentified and anonymously coded.

Results

Twenty-nine percent of the 155 respondents exposed to burn pits self-reported seeing blood in their urine. The average index score of our modified American Urological Association Symptom Index Survey was 12.25 (SD, 7.48). High rates of urinary frequency (84%) and urgency (76%) were self-reported. Bladder, kidney, or lung cancers were self-reported in 3.87%.

Conclusions

US veterans exposed to burn pits are self-reporting hematuria and other lower urinary tract symptoms.
Treatment of donor-specific anti-HLA antibodies-mediated rejection after liver transplantation: A French nationwide retrospective study
Authors: Dumortier Jérôme , Conti Filomena , Hiriart Jean-Baptiste , Dharancy Sébastien , Duvoux Christophe , Besch Camille , Houssel-Debry Pauline , Latournerie Marianne , Chermak Faiza , Meszaros Magdalena , Pageaux Georges-Philippe , Radenne Sylvie , Boillot Olivier , Hardwigsen Jean , Kounis Ilias , Kamar Nassim , Saliba Faouzi , Erard Domitille , Del Bello Arnaud
Published: June 2023

The deleterious effect of donor-specific anti-HLA antibodies (DSA) after liver transplantation (LT) has been increasingly recognized during the past decade. Antibody-mediated rejection (AMR) represents a rare but severe complication in the presence of DSA. However, little is known concerning the treatment of AMR after LT. The nationwide French study aimed to describe LT recipients who received specific treatment of AMR. We performed a multicenter retrospective study on 44 patients who were treated with B-cell targeting agents from January 2008 to December 2020. Median patient age at the time of AMR treatment was 51.6 years (range: 17.9–68.0). AMR was classified as acute (n = 19) or chronic (n = 25). The diagnosis of AMR was made after a median time of 16.8 months (range: 0.4–274.2) after LT. The main therapeutic combination was plasma exchange/rituximab/IVIG (n = 25, 56.8%). The median follow-up after the treatment of AMR was 32 months (range: 1–115). After the treatment, 1-, 5- and 10-year patient and graft survivals were 77%, 55.9%, and 55.9%, and 69.5%, 47.0%, and 47.0%, respectively. Initial total bilirubin (Q1–Q3 vs. Q4) was significantly associated with patient survival (log-rank test, p = 0.005) and graft survival (log-rank test, p = 0.002). After a median follow-up of 21 months (range: 12–107), DSA became undetectable in 15/38 patients (39.5%) with available DSA monitoring. In conclusion, specific treatment of AMR in LT recipients has slowly emerged in France during the past decade and has probably been considered in the most severe patients; this explains the global poor outcome, even if the outcome was favorable in some cases.
The Impact of Daily Processor Use on Adult Cochlear Implant Outcomes: Reexamining the Roles of Duration of Deafness and Age at Implantation
Authors: DeFreese Andrea J. , Lindquist Nathan R. , Shi Linjie , Holder Jourdan T. , Berg Katelyn A. , Haynes David S. , Gifford René H.
Published: June 2023

Objective

To quantify the roles and relationships between age at implantation, duration of deafness (DoD), and daily processor use via data logging on speech recognition outcomes for postlingually deafened adults with cochlear implants.

Study Design

Retrospective case review.

Setting

Cochlear implant (CI) program at a tertiary medical center.

Patients

Six-hundred fourteen postlingually deafened adult ears with CIs (mean age, 63 yr; 44% female) were included.

Main Outcome Measure(s)

A stepwise multiple regression analysis was completed to investigate the combined effects of age, DoD, and daily processor use on CI-aided speech recognition (Consonant-Nucleus-Consonant monosyllables and AzBio sentences).

Results

Results indicated that only daily processor use was significantly related to Consonant-Nucleus-Consonant word scores (R
2 = 0.194, p < 0.001) and AzBio in quiet scores (R
2 = 0.198, p < 0.001), whereas neither age nor DoD was significantly related. In addition, there was no significant relationship between daily processor use, age at implantation, or DoD and AzBio sentences in noise (R
2 = 0.026, p = 0.005).

Conclusions

Considering the clinical factors of age at implantation, DoD, and daily processor use, only daily processor use significantly predicted the ~20% of variance in postoperative outcomes (CI-aided speech recognition) accounted for by these clinical factors.
Deep Learning Models for Severity Prediction of Acute Pancreatitis in the Early Phase From Abdominal Nonenhanced Computed Tomography Images
Authors: Chen Zhiyao , Wang Yi , Zhang Huiling , Yin Hongkun , Hu Cheng , Huang Zixing , Tan Qingyuan , Song Bin , Deng Lihui , Xia Qing
Published: June 2023

Objectives

To develop and validate deep learning (DL) models for predicting the severity of acute pancreatitis (AP) by using abdominal nonenhanced computed tomography (CT) images.

Methods

The study included 978 AP patients admitted within 72 hours after onset and performed abdominal CT on admission. The image DL model was built by the convolutional neural networks. The combined model was developed by integrating CT images and clinical markers. The performance of the models was evaluated by using the area under the receiver operating characteristic curve.

Results

The clinical, Image DL, and the combined DL models were developed in 783 AP patients and validated in 195 AP patients. The combined models possessed the predictive accuracy of 90.0%, 32.4%, and 74.2% for mild, moderately severe, and severe AP. The combined DL model outperformed clinical and image DL models with 0.820 (95% confidence interval, 0.759–0.871), the sensitivity of 84.76% and the specificity of 66.67% for predicting mild AP and the area under the receiver operating characteristic curve of 0.920 (95% confidence interval, 0.873–0.954), the sensitivity of 90.32%, and the specificity of 82.93% for predicting severe AP.

Conclusions

The DL technology allows nonenhanced CT images as a novel tool for predicting the severity of AP.
Pathways From HIV-Related Stigma, Racial Discrimination, and Gender Discrimination to HIV Treatment Outcomes Among Women Living With HIV in Canada: Longitudinal Cohort Findings
Authors: Malama Kalonde , Logie Carmen H. , Sokolovic Nina , Skeritt Lashanda , O'Brien Nadia , Cardinal Claudette , Gagnier Brenda , Loutfy Mona , Kaida Angela , de Pokomandy Alexandra
Published: June 2023

Background:

HIV-related stigma, gender discrimination, and racial discrimination harm mental health and hamper HIV treatment access for women living with HIV. Maladaptive coping strategies, such as substance use, can further worsen HIV treatment outcomes, whereas resilience can improve HIV outcomes. We examined resilience and depression as mediators of the relationship between multiple stigmas and HIV treatment outcomes among women living with HIV.

Setting:

Ontario, British Columbia, and Quebec, Canada.

Methods:

We conducted a longitudinal study with 3 waves at 18-month intervals. We used structural equation modeling to test the associations of multiple stigmas (HIV-related stigma, racial discrimination, and gender discrimination) or an intersectional construct of all 3 stigmas at wave 1 on self-reported HIV treatment cascade outcomes (≥95% antiretroviral treatment [ART] adherence, undetectable viral load) at wave 3. We tested depression and resilience at wave 2 as potential mediators and adjusted for sociodemographic factors.

Results:

There were 1422 participants at wave 1, half of whom were Black (29%) or Indigenous (20%). Most participants reported high ART adherence (74%) and viral suppression (93%). Racial discrimination was directly associated with having a detectable viral load, while intersectional stigma was directly associated with lower ART adherence. Resilience mediated associations between individual and intersectional stigmas and HIV treatment cascade outcomes, but depression did not. Racial discrimination was associated with increased resilience, while intersectional and other individual stigmas were associated with reduced resilience.

Conclusion:

Race, gender and HIV-related stigma reduction interventions are required to address intersectional stigma among women living with HIV. Including resilience-building activities in these interventions may improve HIV treatment outcomes.
An update on hormonal regulation of early embryo-fallopian tube interactions: insights for improvements of assisted reproductive technology outcomes
Authors: Kodithuwakku Suranga P. , Ng Ernest H. Y. , Yeung William S. B. , Lee Kai-Fai
Published: June 2023

Human fallopian tubes (FTs) play important roles in the whole reproductive process. FTs are the site for the final maturation of gametes, fertilization, transport of preimplantation embryos, and early embryonic development before entering the uterus. All these functions are critical in the establishment of a successful pregnancy. When the embryo is in transit through the FT, the FT microenvironment changes through endocrine, paracrine, autocrine, and juxtacrine mechanisms which involve various hormones and bioactive substances mainly from the neighboring cells. Therefore, the interactions between the embryo and the FT may be the earliest embryo-maternal communications that are essential for the establishment of pregnancy. This review critically discusses the evidence of various hormonal and bioactive mediated control of the microenvironment in the FTs during the earliest embryo-maternal communications. Moreover, we highlight existing gaps in the knowledge and the importance of exploring more of the physiology of FTs which will hold the key to producing high-quality embryos for patients seeking in vitro fertilization (IVF) treatments.
Modified Drilled Extended Spreader Grafts in Asian Rhinoplasty: Clinical Application and Histopathological Analysis
Authors: Xu Yihao , Song Zhen , Zhang Xulong , Guo Junsheng , Tian Le , Zheng Ruobing , Wang Huan , You Jianjun , Fan Fei
Published: June 2023

Background:

Extended Spreader Grafts (ESGs) are widely used for both esthetic and functional purpose in rhinoplasty. This study aims to examine the effects of drilling on ESGs in rhinoplasty and their clinical benefits, as well as to analyze their histologic characteristics.

Methods:

We conducted a retrospective review of patients undergoing esthetic rhinoplasty using drilled ESGs with autologous costal cartilage by a senior surgeon from January 2018 to April 2022.

Results:

A total of 80 patients were included, with a mean follow-up period of 26 months. Revision operations were performed on 4 patients. The phenomenon of tissue ingrowth from the septum mucoperichondrium to the septal cartilage through the holes of the drilled ESGs was observed in all 4 patients. Specimens of the ingrown tissue were taken from 3 patients during their revision surgeries. Vascular structures and connective tissue were observed in the specimens after fixation, paraffin embedding, and staining with hematoxylin-eosin. No other complications were observed except for 2 cases presenting cartilage warping after surgery.

Conclusion:

Application of the drilled ESGs is a simple but effective approach, which has 3 significant advantages in rhinoplasty: enhancing the stability of the cartilaginous framework through connective tissue ingrowth, preserving the septal cartilage, and providing septum vitality by allowing the formation of vascular structures between the perichondrium and the septal cartilage; reducing the probability of warping in early stages through release the tension force of the cartilage itself.

Level of Evidence:

Level IV.
GRPa-PRS: A risk stratification method to identify genetically-regulated pathways in polygenic diseases
Authors: Li Xiaoyang , Fernandes Brisa S. , Liu Andi , Chen Jingchun , Chen Xiangning , Zhao Zhongming , Dai Yulin
Published: June 2023

Background

Polygenic risk scores (PRS) are tools used to evaluate an individual’s susceptibility to polygenic diseases based on their genetic profile. A considerable proportion of people carry a high genetic risk but evade the disease. On the other hand, some individuals with a low risk of eventually developing the disease. We hypothesized that unknown counterfactors might be involved in reversing the PRS prediction, which might provide new insights into the pathogenesis, prevention, and early intervention of diseases.

Methods

We built a novel computational framework to identify genetically-regulated pathways (GRPas) using PRS-based stratification for each cohort. We curated two AD cohorts with genotyping data; the discovery (disc) and the replication (rep) datasets include 2722 and 2854 individuals, respectively. First, we calculated the optimized PRS model based on the three recent AD GWAS summary statistics for each cohort. Then, we stratified the individuals by their PRS and clinical diagnosis into six biologically meaningful PRS strata, such as AD cases with low/high risk and cognitively normal (CN) with low/high risk. Lastly, we imputed individual genetically-regulated expression (GReX) and identified differential GReX and GRPas between risk strata using gene-set enrichment and variational analyses in two models, with and withoutAPOEeffects. An orthogonality test was further conducted to verify those GRPas are independent of PRS risk. To verify the generalizability of other polygenic diseases, we further applied a default model of GRPa-PRS for schizophrenia (SCZ).

Results

For each stratum, we conducted the same procedures in both the disc and rep datasets for comparison. In AD, we identified several well-known AD-related pathways, including amyloid-beta clearance, tau protein binding, and astrocyte response to oxidative stress. Additionally, we discovered resilience-related GRPs that are orthogonal to AD PRS, such as the calcium signaling pathway and divalent inorganic cation homeostasis. In SCZ, pathways related to mitochondrial function and muscle development were highlighted. Finally, our GRPa-PRS method identified more consistent differential pathways compared to another variant-based pathway PRS method.

Conclusions

We developed a framework, GRPa-PRS, to systematically explore the differential GReX and GRPas among individuals stratified by their estimated PRS. The GReX-level comparison among those strata unveiled new insights into the pathways associated with disease risk and resilience. Our framework is extendable to other polygenic complex diseases.
Service delivery in acute ischemic stroke patients: Does sex matter?
Authors: Medlin Friedrich , Strambo Davide , Lambrou Dimitris , Caso Valeria , Michel Patrik
Published: June 2023

Background

Women with acute ischemic stroke (AIS) are older and have higher preexisting handicap than men. Given that these factors do not fully explain their poorer long-term outcomes, we sought to investigate potential sex differences in the delivery of acute stroke care in a large cohort of consecutive AIS patients.

Methodss

We analyzed all patients from the Acute STroke Registry and Analysis of Lausanne (ASTRAL) from 03/2003-12/2019. Multivariate analyses were performed on acute time metrics, revascularization therapies, ancillary exams for stroke work-up, subacute symptomatic carotid artery revascularization, frequency of change in goals of care (palliative care) and length of hospital stay.

Results

Of the 5347 analyzed patients, 45% were biologically female and the median age was 74.6 years. After multiple adjustments, female sex was significantly associated with higher onset-to-door (adjusted hazard ratio (aHR):1.09, 95% confidence interval (CI) 1.04-1.14) and door-to-endovascular-puncture intervals (aHR:1.15, 95%CI:1.05-1.25). Women underwent less diagnostic exams (adjusted odds ratio (aOR): 0.94, 95%CI:0.85-1.04), fewer subacute carotid revascularizations (aOR:0.69, 95% CI:0.33-1.18) and had longer hospital stays (aHR:1.03, 95%CI:0.99-1.07), but these differences were not statistically significant. We found no differences in the rates of acute revascularization treatments, or in the frequency of change of goals of treatments.

Conclusions

In this retrospective analysis of a large, consecutive AIS cohort, female sex was associated with unfavorable pre- and inhospital time metrics, and lesser diagnostic exam and carotid revascularization rates. Such indicators of less effective stroke care delivery may contribute to the poorer long-term functional outcomes in female patients and require further attention.
MATERNAL DETERMINANTS OF ADVERSE NEONATAL OUTCOMES IN A RURAL DISTRICT HOSPITAL IN EAST AFRICA
Authors: Ogah Adenike Oluwakemi , Ogbole James Aaron
Published: June 2023

Background

Maternal predisposing factors to adverse birth outcomes are often times assumed to be similar in rural and urban settings. This assumption have led to many failed or failing interventions. This study investigated the maternal risk factors of adverse birth outcomes in a remote community and compared with existing literature of similar studies done in urban areas or developed settings.

Subject and methods

This was the baseline data of a prospective cohort study, carried out in Gitwe village, Rwanda, 2019. Healthy, 529 mother-singleton infant pairs were recruited consecutively from Gitwe district hospital.

Results

The burden of adverse neonatal outcomes of significance in this rural study (cesarean section delivery, low birth weight, small for gestational age and prematurity) were 38.8%, 10.6%, 21.4% and 4.9%, respectively. Significant (p<0.05) maternal characteristics associated with cesarean section delivery were obesity, high number of antenatal visits (>6), non-christian religion, university education, entrepreneurs, positive HIV status and short stature. Unmarried mothers were likely to produce LBW and preterm babies, while primips were prone to deliver SGA babies. The magnitude of adverse birth outcomes in this rural study was unexpectedly higher than what exist at and their drivers were not exactly the same as in urban settings and at national level.

Conclusion and Recommendations

The burden of adverse birth outcomes in this study was higher than that of several countries in the world. Therefore, mothers (not neglecting their marital, HIV, parity and religion status), residing in these rural areas should be priortised for health care interventions, in order to lower the short-and long-term effects of these adverse birth outcomes.
Identification of novel variants, genes and pathways potentially linked to Parkinson’s disease using machine learning
Authors: Yu Eric , Larivière Roxanne , Thomas Rhalena A. , Liu Lang , Senkevich Konstantin , Rahayel Shady , Trempe Jean-François , Fon Edward A. , Gan-Or Ziv
Published: June 2023

There are 78 loci associated with Parkinson’s disease (PD) in the most recent genome-wide association study (GWAS), yet the specific genes driving these associations are mostly unknown. Herein, we aimed to nominate the top candidate gene from each PD locus, and identify variants and pathways potentially involved in PD. We trained a machine learning model to predict PD-associated genes from GWAS loci using genomic, transcriptomic, and epigenomic data from brain tissues and dopaminergic neurons. We nominated candidate genes in each locus, identified novel pathways potentially involved in PD, such as the inositol phosphate biosynthetic pathway (INPP5F,IP6K2,ITPKB, PPIP5K2). Specific common coding variants inSPNS1andMLXmay be involved in PD, and burden tests of rare variants further support thatCNIP3,LSM7,NUCKS1and the polyol/inositol phosphate biosynthetic pathway are associated with PD. Functional studies are needed to further analyze the involvements of these genes and pathways in PD.
Improving irregular temporal modeling by integrating synthetic data to the electronic medical record using conditional GANs: a case study of fluid overload prediction in the intensive care unit
Authors: Rafiei Alireza , Rad Milad Ghiasi , Sikora Andrea , Kamaleswaran Rishikesan
Published: June 2023

Objective

The challenge of irregular temporal data, which is particularly prominent for medication use in the critically ill, limits the performance of predictive models. The purpose of this evaluation was to pilot test integrating synthetic data within an existing dataset of complex medication data to improve machine learning model prediction of fluid overload.

Materials and Methods

This retrospective cohort study evaluated patients admitted to an ICU≥72 hours. Four machine learning algorithms to predict fluid overload after 48-72 hours of ICU admission were developed using the original dataset. Then, two distinct synthetic data generation methodologies (synthetic minority over-sampling technique (SMOTE) and conditional tabular generative adversarial network (CT-GAN)) were used to create synthetic data. Finally, a stacking ensemble technique designed to train a meta-learner was established. Models underwent training in three scenarios of varying qualities and quantities of datasets.

Results

Training machine learning algorithms on the combined synthetic and original dataset overall increased the performance of the predictive models compared to training on the original dataset. The highest performing model was the metamodel trained on the combined dataset with 0.83 AUROC while it managed to significantly enhance the sensitivity across different training scenarios.

Discussion

The integration of synthetically generated data is the first time such methods have been applied to ICU medication data and offers a promising solution to enhance the performance of machine learning models for fluid overload, which may be translated to other ICU outcomes. A meta-learner was able to make a trade-off between different performance metrics and improve the ability to identify the minority class.
Genetic relationships between chronic pain, psychopathologies, and neuroticism
Authors: Zorina-Lichtenwalter Katerina , Bango Carmen I. , Čeko Marta , Ashar Yoni K. , Keller Matthew C. , Wager Tor D. , Friedman Naomi P.
Published: June 2023

Chronic pain and psychiatric conditions have consistently demonstrated substantial overlap in risk factors, epidemiology, and effective treatments. Previous work has identified cross-condition latent factors underlying shared genetic risk for several distinct psychiatric conditions and pain conditions. Here, we sought to examine the relationships between these latent genetic factors to determine biological mechanisms common to both pain and psy-chiatric conditions. We combined two previously published genetic struc-turl equation models. The first model consisted of 24 pain conditions and their two latent factors: General and Musculoskeletal pain-specific. The second model consisted of 11 psychiatric conditions and their four latent factors: Externalizing, Internalizing, Compulsive Thought, and Psychotic Thought. The combined model of six factors and 35 conditions allowed us to estimate correlations between all factors and between conditions of one domain (pain) and factors of the other (psychiatric). We then added three measures of neuroticism (depressive affect subscale, worrying subscale, and total neuroticism score) to this model to examine correlations with all conditions and factors and test for possible explanation of pain-mental disorder relationships by neuroticism. We found that genetic associations between pain and psychiatric conditions were selective to the General Pain factor (and not Musculoskeletal) and Internalizing and Externalizing, but not Thought disorder factors. Neuroticism was associated with pain conditions to the extent that they loaded onto the General Pain factor (i.e., were associated with other pain conditions). Neuroticism also explained a substantial proportion of shared genetic variance between General Pain and Externalizing and between General Pain and Internalizing factors. Overall, the genetic risks shared among chronic pain and psychiatric conditions and neuroticism suggest shared biological mechanisms and underscore the importance of clinical assessment and treatment programs that leverage these commonalities.
The geography of metacommunities: landscape characteristics drive geographic variation in the assembly process through selecting species pool attributes
Authors: Khattar Gabriel , Peres-Neto Pedro
Published: June 2023

Metacommunity ecology traditionally disregards that the dominant life-histories observed in species pools are selected by the characteristics of landscapes where the assembly process takes place. Recognizing the importance of this relationship is relevant because it integrates macroecological principles into metacommunity theory, generating a greater understanding about the ecological causes underlying broad-scale geographic variation in the relative importance of assembly mechanisms. To demonstrate that, we employed simulation models in which species pools with the same initial distribution of niche breadths and dispersal abilities interacted in landscapes with contrasting characteristics. By assessing the traits of species that dominated the metacommunity in each landscape type, we determined how different landscape characteristics select for different life-history strategies at the metacommunity level. We also analyzed the simulated data to derive predictions about the causal links between landscape characteristics, dominant life-histories in species pools, and their mutual influence on empirical inferences about the assembly process. We provide empirical support to these predictions by contrasting the assembly process of moth metacommunities in a tropical versus a temperate mountainous landscape. Collectively, our simulation models and empirical analyses illustrate how our framework can be formalized as an inferential tool for investigating the geography of metacommunity assembly.
Vascular Endothelial Barrier Protection Prevents Atrial Fibrillation by Preserving Cardiac Nanostructure
Authors: Mezache Louisa , Soltisz Andrew , Johnstone Scott R. , Isakson Brant E. , Veeraraghavan Rengasayee
Published: June 2023

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting ∼3% of the US population. It is widely associated with inflammation, vascular dysfunction, and elevated levels of the vascular leak-inducing cytokine, vascular endothelial growth factor (VEGF). The mechanism underlying AF is not well understood and current treatments are limited to managing this progressive disease, rather than arresting the underlying pathology. We previously identified edema-induced disruption of sodium channel (NaV1.5) –rich intercalated disk (ID) nanodomains as a novel mechanism for AF initiation secondary to acute inflammation. Therefore, we hypothesized that protecting the vascular barrier can prevent vascular leak-induced atrial arrhythmias. We identified two molecular targets for vascular barrier protection, connexin43 (Cx43) hemichannels and pannexin-1 (Panx1) channels, which have been implicated in cytokine-induced vascular leak. AF incidence was increased in untreated mice exposed to VEGF relative to vehicle controls. VEGF also increased the average number of AF episodes. VEGF shifted NaV1.5 signal to longer distances from Cx43 gap junctions (GJs), measured by a distance transformation-based spatial analysis of 3D confocal images of IDs. Similar effects were observed with NaV1.5 localized near mechanical junctions (MJs) composed of N-cad. Blocking connexin43 hemichannels (αCT11 peptide) or Panx1 channels (PxIL2P peptide) significantly reduced the duration of AF episodes compared to VEGF alone with no treatment. Concurrently, both peptide therapies preserved NaV1.5 distance from GJs to control levels and reduced MJ-adjacent intermembrane distance in these hearts. Notably, similar antiarrhythmic efficacy was also achieved with clinically-relevant small molecule inhibitors of Cx43 and Panx1.
Non-Consummatory Behavior Signals Predict Aversion-Resistant Alcohol Drinking in Head-Fixed Mice
Authors: Timme Nicholas M. , Ardinger Cherish E. , Weir Seth D. C. , Zelaya-Escobar Rachel , Kruger Rachel , Lapish Christopher C.
Published: June 2023

A key facet of alcohol use disorder is continuing to drink alcohol despite negative consequences (so called “aversion-resistant drinking”). In this study, we sought to assess the degree to which head-fixed mice exhibit aversion-resistant drinking and to leverage behavioral analysis techniques available in head-fixture to relate non-consummatory behaviors to aversion-resistant drinking. We assessed aversion-resistant drinking in head-fixed female and male C57BL/6J mice. We adulterated 20% (v/v) alcohol with varying concentrations of the bitter tastant quinine to measure the degree to which mice would continue to drink despite this aversive stimulus. We recorded high-resolution video of the mice during head-fixed drinking, tracked body parts with machine vision tools, and analyzed body movements in relation to consumption. Female and male head-fixed mice exhibited heterogenous levels of aversion-resistant drinking. Additionally, non-consummatory behaviors, such as paw movement and snout movement, were related to the intensity of aversion-resistant drinking. These studies demonstrate that head-fixed mice exhibit aversion-resistant drinking and that non-consummatory behaviors can be used to assess perceived aversiveness in this paradigm. Furthermore, these studies lay the groundwork for future experiments that will utilize advanced electrophysiological techniques to record from large populations of neurons during aversion-resistant drinking to understand the neurocomputational processes that drive this clinically relevant behavior.