bluuebunny/crossref_metadata_2025 huggingface dataset:
The pathological mechanisms and novel therapeutics for Leber’s hereditary optic neuropathy
Authors: Yang Yi-Ping , Foustine Shania , Hsiao Yu-Jer , Tsai En-Tung , Tsai Fu-Ting , Wang Chia-Lin , Ko Yu-Ling , Tai Hsiao-Yun , Tsai Yi-Ching , Yang Chang-Hao , Fu Yun-Ju , Wang An-Guor , Chien Yueh
Published: April 2023

Optic neuropathies were estimated to affect 115 in 100,000 population in 2018. Leber’s Hereditary Optic Neuropathy (LHON) as one of such optic neuropathy diseases that was first identified in 1871 and can be defined as a hereditary mitochondrial disease. LHON is associated with three mtDNA point mutations which are G11778A, T14484, and G3460A that affect the NADH dehydrogenase subunits of 4, 6, and 1, respectively. However, in most cases, only one point mutation is involved. Generally, in manifestation of the disease, there are no symptoms until the terminal dysfunction in the optic nerve is observed. Due to the mutations, nicotinamide adenine dinucleotide (NADH) dehydrogenase or complex I is absent and thus ATP production is stopped. This further causes the generation of reactive oxygen species and retina ganglion cells apoptosis. Aside from the mutations, there are several environmental factors such as smoking and alcohol consumption that can be pointed out as the risk factors of LHON. Nowadays, gene therapy has been intensively studied for LHON treatment. Disease models using human induced pluripotent stem cells (hiPSCs) have been utilized for LHON research.
How Does Environmental Temperature Affect Farmworkers’ Work Rates in the California Heat Illness Prevention Study?
Authors: Langer Chelsea E. , Armitage Tracey L. , Beckman Stella , Tancredi Daniel J. , Mitchell Diane C. , Schenker Marc B.
Published: April 2023

Objective

Estimate the association between environmental temperature (wet bulb globe temperature [WBGT]) and work rate over the course of a workday.

Methods

Repeated-measures regression was used to identify characteristics impacting work rate in a cross-sectional study of Latino farmworkers. Minute-by-minute work rate (measured by accelerometer) and WBGT were averaged over 15-minute intervals.

Results

Work rate decreased by 4.34 (95% confidence interval [CI], −7.09 to −1.59) counts per minute per degree Celsius WBGT in the previous 15-minute interval. Cumulative quarter hours worked (2.13; 95% CI, 0.82 to 3.45), age (−3.64; 95% CI, −4.50 to −2.79), and dehydration at the end of workday (51.37; 95% CI, 19.24 to 83.50) were associated with counts per minute as were gender, pay type (piece rate vs hourly) and body mass index ≥25 kg/m2. The effects of pay type and body mass index were modified by gender.

Conclusion

Increased temperature was associated with a decrease in work rate.
Efficacy of peripheral electrical nerve stimulation on improvements of urodynamics and voiding diary in patients with neurogenic lower urinary tract dysfunction: a systematic review and meta-analysis
Authors: Ge Qingyu , Xu Hewei , Fan Zongyao , Li Weilong , Chen Zhengsen , Yue Dezhou , Xu Jie , Zhang Sicong , Xue Jun , Shen Baixin , Wei Zhongqing
Published: April 2023

Background:

Peripheral electrical nerve stimulation is a routinely recommended treatment for non-neurogenic overactive bladder but has not been approved for patients with neurogenic lower urinary tract dysfunction (NLUTD). This systematic review and meta-analysis was to elucidate the efficacy and safety of electrostimulation and thus provide firm evidence for treating NLUTD.

Materials and methods:

We systematically performed the literature search through PubMed, Web of Science, and Cochrane Library databases in March 2022. The eligible studies were identified across the inclusion criteria and the data on urodynamic outcomes, voiding diary parameters, and safety was collected to quantitatively synthesize the pooled mean differences (MDs) with 95% CIs. Subgroup analyses and sensitivity analyses were subsequently used to investigate the possible heterogeneity. This report was achieved in accordance with the preferred reporting items for systematic reviews and meta-analyses statement.

Results:

A total of 10 studies involving 464 subjects and 8 studies with 400 patients were included for systematic review and meta-analysis, respectively. The pooled effect estimates indicated that electrostimulation could significantly improve urodynamic outcomes, including maximum cystometric capacity (MD=55.72, 95% CI 15.73, 95.72), maximum flow rate (MD=4.71, 95% CI 1.78, 7.65), maximal detrusor pressure (MD=−10.59, 95% CI −11.45, −9.73), voided volume (MD=58.14, 95% CI 42.97, 73.31), and post-void residual (MD=−32.46, 95% CI −46.63, −18.29); for voiding diary parameters, patients undergoing electrostimulation showed lower MDs of incontinence episodes per 24 h (MD=−2.45, 95% CI −4.69, −0.20) and overactive bladder symptom score (MD=−4.46, 95% CI −6.00, −2.91). In addition to surface redness and swelling, no stimulation-related severe adverse events were reported else.

Conclusions:

The current evidence demonstrated that peripheral electrical nerve stimulation might be effective and safe for managing NLUTD, whereas more reliable data from large-scale randomized controlled trials are necessary to strengthen this concept.
Does one-anastomosis gastric bypass provide better outcomes than sleeve gastrectomy in patients with BMI greater than 50? A systematic review and meta-analysis
Authors: Barzin Maryam , Ebadinejad Amir , Aminian Ali , Khalaj Alireza , Ghazy Faranak , Koohi Fatemeh , Hosseinpanah Farhad , Ramezani Ahmadi Amirhossein , Valizadeh Majid , Abiri Behnaz
Published: April 2023

In patients with BMI greater than 50, sleeve gastrectomy (SG) may not be adequate to treat obesity. To determine whether one-anastomosis gastric bypass (OAGB) can provide better outcomes compared with SG in patients with BMI greater than 50, a systematic review and meta-analysis was conducted, including a total of nine retrospective studies with a total of 2332 participants. There was a significant difference in the percentage of excess weight loss [weighted mean difference (WMD): 8.52; 95% CI: 5.81–11.22; P<0.001) and percentage of total weight loss (WMD: 6.65; 95% CI: 5.05–8.24; P<0.001). No significant differences were seen in operative time (WMD: 1.91; 95% CI: −11.24 to 15.07; P=0.77) and length of stay in hospital (WMD: −0.41; 95% CI: −1.18 to 0.37; P=0.30) between the two groups. There were no significant differences between OAGB with SG in Clavien–Dindo grades I–III [odds ratio (OR): 1.56; 95% CI: 0.80–3.05], or grade IV complications (OR: 0.72; 95% CI: 0.18–2.94). The meta-analysis on remission of type 2 diabetes indicated a comparable effect between SG and OAGB (OR: 0.77; 95% CI: 0.28–2.16). The OAGB group had a significantly higher rate of remission of hypertension compared with the SG group (OR: 1.63; 95% CI: 1.06–2.50). The findings of this meta-analysis suggest that the OAGB accomplished a higher percentage of total weight loss and percentage of excess weight loss at short-term and mid-term follow-up but, there was no major difference between the OAGB and SG operations in terms of perioperative outcomes, complications, and diabetes remission.
Microneedles Facilitate Small-Volume Intracochlear Delivery Without Physiologic Injury in Guinea Pigs
Authors: Leong Stephen , Feng Sharon J. , Aksit Aykut , Olson Elizabeth S. , Kysar Jeffrey W. , Lalwani Anil K.
Published: April 2023

Hypothesis

Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full reconstitution of the RWM within 48 hours.

Background

We have developed polymeric microneedles that allow for in vivo perforation of the guinea pig RWM and aspiration of perilymph for diagnostic analysis, with full reconstitution of the RWM within 48 to 72 hours. In this study, we investigate the ability of microneedles to deliver precise volumes of therapeutics into the cochlea and assess the subsequent consequences on hearing.

Methods

Volumes of 1.0, 2.5, or 5.0 μL of artificial perilymph were injected into the cochlea at a rate of 1 μL/min. Compound action potential (CAP) and distortion product otoacoustic emission were performed to assess for hearing loss (HL), and confocal microscopy was used to evaluate the RWM for residual scarring or inflammation. To evaluate the distribution of agents within the cochlea after microneedle-mediated injection, 1.0 μL of FM 1–43 FX was injected into the cochlea, followed by whole mount cochlear dissection and confocal microscopy.

Results

Direct intracochlear injection of 1.0 μL of artificial perilymph in vivo, corresponding to about 20% of the scala tympani volume, was safe and did not result in HL. However, injection of 2.5 or 5.0 μL of artificial perilymph into the cochlea produced statistically significant high-frequency HL persisting 48 hours postperforation. Assessment of RWMs 48 hours after perforation revealed no inflammatory changes or residual scarring. FM 1–43 FX injection resulted in distribution of the agent predominantly in the basal and middle turns.

Conclusion

Microneedle-mediated intracochlear delivery of small volumes relative to the volume of the scala tympani is feasible, safe, and does not cause HL in guinea pigs; however, injection of large volumes induces high-frequency HL. Injection of small volumes of a fluorescent agent across the RWM resulted in significant distribution within the basal turn, less distribution in the middle turn, and almost none in the apical turn. Microneedle-mediated intracochlear injection, along with our previously developed intracochlear aspiration, opens the pathway for precision inner ear medicine.
Application of an Intraoperative Auditory Brainstem Response Measurement System in Active Middle Ear Implant Revision Surgery
Authors: Rak Kristen , Köstler Carolina , Geiger Ute , Kaulitz Stefan , Herrmann David , Shehata-Dieler Wafaa , Hagen Rudolf , Cebulla Mario
Published: April 2023

Objective

To investigate the benefit of intraoperative auditory brainstem response (ABR) measurements in revision active middle ear implant surgery.

Study design

Retrospective data analysis.

Setting

Tertiary referral center with a large active middle ear implant program.

Main outcome measures

Intraoperative ABR thresholds, audiogram, sound field thresholds, speech understanding in the Freiburger monosyllabic word test.

Patients

Fourteen patients with active middle ear implant revision surgery.

Results

The application of the ABR measurement resulted in improved sound field thresholds and enhanced speech understanding. Analysis revealed a significant correlation of intraoperative gain in ABR threshold with the postoperative gain in sound field thresholds.

Conclusion

ABR monitoring can be a useful tool to provide information intraoperatively about the coupling efficiency of the FMT. Especially in revision surgeries, this might help to improve postoperative hearing success.
The Effect of Aging on Auditory Nerve Function: Insights from Intraoperative eCAP Recordings in Cochlear Implant Users
Authors: Mussoi Bruna S. , Woodson Erika , Sydlowski Sarah
Published: April 2023

Background

Advanced age is associated with poorer speech perception outcomes in cochlear implant (CI) users. In an effort to improve our understanding of the basis for this decline, this study focused on the contributions from peripheral auditory processing, using the electrically evoked compound action potential (eCAP).

Objectives

To investigate the effect of aging on intraoperative, suprathreshold eCAP responses (amplitude growth function [AGF] slopes, eCAP maximum amplitudes, and N1 latencies) across the electrode array, in a large cohort of recipients of newer generation devices, who met hearing preservation criteria.

Methods

Participants of this retrospective study consisted of 113 middle-aged and older CI recipients. Intraoperative eCAP measures consisted of AGF slopes, maximum amplitudes, and N1 latencies at the maximum amplitude. eCAP recordings were obtained at several intracochlear electrodes, which were grouped by electrode location (basal, middle, and apical).

Results

There was a moderate to strong association between suprathreshold eCAP measures (eCAP AGF slopes and maximum amplitudes) and age, particularly for basal and middle electrodes. For apical electrodes, correlations between both suprathreshold eCAP measures and age were weak (and for eCAP maximum amplitudes, not statistically significant). N1 latencies at the maximum amplitudes were not associated with age at any electrode location.

Conclusions

Results of this study add to a growing body of evidence suggesting that aging may negatively affect suprathreshold eCAP responses, especially in basal and middle cochlear regions. Although it is difficult to separate the effects of aging from those of duration of deafness, both would support recommending early implantation in the clinical setting.
Cytotoxicity of Tetracyclines in Human Tympanic Membrane Fibroblasts
Authors: Dirain Carolyn O. , Antonelli Patrick J.
Published: April 2023

Hypothesis

Tetracyclines are less cytotoxic to tympanic membrane (TM) fibroblasts than quinolones.

Background

Use of quinolone ear drops after tympanostomy tube placement and for acute otitis externa has been linked to an increased risk of TM perforation. This has been verified in animal models. Cell culture studies have shown quinolones to be highly toxic to TM fibroblasts. Tetracyclines are a potential alternative to quinolones as they have been used to treat acute otitis externa and are thought to be nontoxic to the inner ear. We aimed to determine if tetracyclines are cytotoxic to TM fibroblasts.

Methods

Human TM fibroblasts were treated with 1:10 dilutions of ofloxacin 0.3%, ciprofloxacin 0.3%, doxycycline 0.3 and 0.5%, minocycline 0.3 and 0.5%, tetracycline 0.3 and 0.5%, or dilute HCl (control), twice within 24 hours or four times within 48 hours. After 2 hours of treatment, cells were returned to growth media. Cells were observed with phase-contrast microscopy until cytotoxicity was measured.

Results

Fibroblasts had lower survival with ciprofloxacin 0.3% and doxycycline 0.5% treatment compared with the control after 24 and 48 hours (all p < 0.0001). Fibroblasts treated with minocycline 0.5% had increased cell survival after 24 hours. Minocycline 0.3 and 0.5% showed increased TM fibroblast survival after 48 hours (all p < 0.0001). Phase-contrast images mirrored the cytotoxicity findings.

Conclusions

Tetracyclines are less toxic to cultured TM fibroblasts than ciprofloxacin. Fibroblast tetracycline toxicity is drug and dose specific. Minocycline shows the most promise for possible otic applications in which fibroblast toxicity is a concern.
Role and mechanism of actin-related protein 2/3 complex signaling in cancer invasion and metastasis: A review
Authors: Zheng Sihan , Qin Fengfeng , Yin Ji , Li Daiying , Huang Yanlin , Hu Lanxin , He Lu , Lv Caifeng , Li Xiaohui , Li Sen , Hu Wenjian
Published: April 2023

The actin 2/3 complex (Arp2/3) regulates actin polymerization and nucleation of actin filaments, is associated with cell motility, and has been shown to play a key role in the invasion and migration of cancer cells. nucleation-promoting factor (NPF) such as N-WASP (neural-WASP famly verprolin-homologous protein family), WAVE (WASP famly verprolin-homologous protein family), and WASH (WASP and Scar homologue) undergo conformational changes upon receipt of multiple upstream signals including Rho family GTPases, cdc42 (Cell division control protein 42 homolog), and phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5 P2) to bind and activate the Arp2/3 complex. Once activated, the Arp2/3 complex forms actin-based membrane protrusions necessary for cancer cells to acquire an invasive phenotype. Therefore, how to influence the invasion and migration of cancer cells by regulating the activity of the Arp2/3 complex has attracted great research interest in recent years. Several studies have explored the effects of phosphorylation modifications of cortactin and several NPFs (Nucleation Promoting Factor) including N-WASP and WAVE on the activity of the Arp2/3 complex and ultimately on cancer cell invasiveness, and have attempted to suggest new strategies for antiinvasive therapy as a result. Other studies have highlighted the potential of targeting genes encoding partial or complete proteins of the Arp2/3 complex as a therapeutic strategy to prevent cancer cell invasion and metastasis. This article reviews the role of the Arp2/3 complex in the development, invasion, and metastasis of different types of cancer and the mechanisms regulating the activity of the Arp2/3 complex.
Cardiometabolic multimorbidity may identify a more severe subset of rheumatoid arthritis, results from a “real-life” study
Authors: Ruscitti Piero , Di Muzio Claudia , Conforti Alessandro , Di Cola Ilenia , Pavlych Viktoriya , Navarini Luca , Currado Damiano , Biaggi Alice , Di Donato Stefano , Marino Annalisa , Lorusso Sebastiano , Ursini Francesco , Giacomelli Roberto , Cipriani Paola
Published: April 2023

This “real-life” cross-sectional study has been designed to describe disease features of rheumatoid arthritis (RA) participants affected by cardiometabolic multimorbidity than those without. Our purpose was also the identification of possible associations between these cardiometabolic diseases and RA clinical characteristics. Consecutive RA participants with and without cardiometabolic multimorbidity were assessed and their clinical characteristics were recorded. Participants were grouped and compared by the presence or not of cardiometabolic multimorbidity (defined as ≥ 2 out of 3 cardiovascular risk factors including hypertension, dyslipidemia, and type 2 diabetes). The possible influence of cardiometabolic multimorbidity on RA features of poor prognosis was assessed. The positivity of anti-citrullinated protein antibodies, presence of extra-articular manifestations, lack of clinical remission, and biologic Disease-Modifying anti-Rheumatic Drugs (bDMARDs) failure were considered as RA features of poor prognosis. In the present evaluation, 757 consecutive RA participants were evaluated. Among them, 13.5% showed cardiometabolic multimorbidity. These were older (P < .001) and characterized by a longer disease duration (P = .023). They were more often affected by extra-articular manifestations (P = .029) and frequently displayed smoking habit (P = .003). A lower percentage of these patients was in clinical remission (P = .048), and they showed a more frequent history of bDMARD failure (P < .001). Regression models showed that cardiometabolic multimorbidity was significantly correlated with RA features of disease severity. They were predictors of anti-citrullinated protein antibodies positivity, of extra-articular manifestations, and of lack of clinical remission, in both univariate and multivariate analyses. Cardiometabolic multimorbidity was significantly associated with a history of bDMARD failure. We described disease features of RA participants with cardiometabolic multimorbidity, identifying a possible more difficult to treat subset, which may need a new management approach to achieve the treatment goal.
Association of body composition with bone mineral density and fractures in Chinese male type 2 diabetes mellitus
Authors: Meng Chuchen , Zhao Dan , Ye Xin-Hua
Published: April 2023

The association between body composition and bone health in men over 50 years with type 2 diabetes mellitus remains unclear. We aimed to investigate how fat and lean mass affect bone health in male patients with diabetes over 50 years. A total of 233 hospitalized male type 2 diabetes mellitus patients with aged 50 to 78 years were enrolled. Lean mass, fat mass and bone mineral density (BMD) were estimated. The clinical fractures were also assessed. Glycosylated hemoglobin, bone turnover markers, and biochemical parameters were measured. The normal BMD group had a higher lean mass index (LMI) and fat mass index (FMI) and lower levels of bone turnover markers. glycosylated hemoglobin was negatively correlated with LMI (r = −0.224, P = .001) and FMI (r = −0.158, P = .02). In partial correlation adjusted for age and body weight, FMI was negatively correlated (r = −0.135, P = .045) with lumbar spine, while LMI was still positively correlated with lumbar spine (R = 0.133, P = .048) and total hip (R = 0.145, P = .031). In multiple regression analysis, LMI was consistently associated with BMD at the spine (β = 0.290, P < .01), hip (β = 0.293, P < .01), and femoral neck (β = 0.210, P = .01), whereas FMI was only positively associated with BMD at the femoral neck (β = 0.162, P = .037). A total of 28 patients diagnosed with diabetic osteoporotic fractures had lower LMI and FMI than their non-fractured counterparts. LMI was negatively associated with fracture, whereas FMI had such an effect only before adjusting for BMD. Lean mass is dominant in maintaining BMD and is a BMD-independent protective factor for diabetic osteoporotic fracture in male patients aged over 50 years. Fat mass in gravity is positively associated with BMD in the femoral neck, which may mediate fracture protection.
Characteristics and intrasubject variation in the respiratory microbiome in interstitial lung disease
Authors: Cho Jun Yeun , Kim Mi Yeon , Kim Ji Hyoun , Kim Eung-Gook , Kim Sun-Hyung , Yang Bumhee , Kang Hyeran , Lee Ki Man , Choe Kang Hyeon , Shin Yoon Mi
Published: April 2023

Recent studies have reported that the lower airway microbiome may play an essential role in the development and progression of interstitial lung disease (ILD). The aim of the current study was to evaluate the characteristics of the respiratory microbiome and intrasubject variation in patients with ILD. Patients with ILD were recruited prospectively for 12 months. The sample size was small (n = 11) owing to delayed recruitment during the COVID-19 pandemic. All subjects were hospitalized and were evaluated by a questionnaire survey, blood sampling, pulmonary function test, and bronchoscopy. Bronchoalveolar lavage fluid (BALF) was obtained at 2 sites, the most and least disease-affected lesions. Sputum collection was also performed. Furthermore, 16S ribosomal RNA gene sequencing was performed using the Illumina platform and indexes of α- and β-diversity were evaluated. Species diversity and richness tended to be lower in the most-affected lesion than in the least-affected lesion. However, taxonomic abundance patterns were similar in these 2 groups. The phylum Fusobacteria was more prevalent in fibrotic ILD than in nonfibrotic ILD. Inter-sample differences in relative abundances were more prominent in BALF versus sputum specimens. Rothia and Veillonella were more prevalent in the sputum than in BALF. We did not detect site-specific dysbiosis in the ILD lung. BALF was an effective respiratory specimen type for evaluating the lung microbiome in patients with ILD. Further studies are needed to evaluate the causal links between the lung microbiome and the pathogenesis of ILD.
Perception of quality of care using patient reported experience measures (PREMs) in a cohort of adults with HIV: A cross-sectional study
Authors: de Lazzari Elisa , Berrocal Leire , Fernández Emma , Laguno Montserrat , Chivite Iván , Torres Berta , González-Cordón Ana , de la Mora Lorena , Ambrosioni Juan , Iniciarte Alexy , Blanco José Luís , Miró Josep Maria , Martínez Esteban , Martínez-Rebollar Maria , Mallolas Josep
Published: April 2023

Human immunodeficiency virus (HIV) infection is considered a chronic disease. Antiretroviral therapy has allowed persons with HIV (PLWHIV) to achieve the 90-90-90 objectives proposed by the World Health Organization for 2020; but an additional challenge is getting an adequate health-related quality of life. A determining factor in the health-related quality of life of PLWHIV is the health care they perceive to receive. In this sense, we aimed to assess the perception of the outpatient care provided and to identify possible areas for improvement in a single-center, cross-sectional study at the HIV unit of Hospital Clínic, Barcelona. We sought patient reported experience measures by an anonymous e-survey with 11 statements based on a 1 to 6 Likert scale, and a final question measuring user satisfaction and loyalty through the Net Promoter Score (NPS). All PLWHIV with at least a clinical visit between January 1, 2020 and October 14, 2021 were invited. Of 5493 PLWHIV e-mailed, 1633 (30%) responded to the survey. The overall evaluation of clinical care was very favorable. The evaluation of the physical environment and facilities and the time spent in the waiting room received the lowest scores. According to the Net Promoter Score test results, 66% of respondents were willing to recommend this service, and 11% were not. Thus, monitoring patient reported experience measures in PLWHIV actively receiving outpatient care in our hospital allowed to identify the users’ perception on quality of the care received, to determine the rate of satisfaction with the care, and to identify areas for improvement.
Accuracy of percutaneous pedicle screw placement with 3-dimensional fluoroscopy-based navigation: Lateral decubitus position versus prone position
Authors: Okuda Ryuichiro , Ikuma Hisanori , Inoue Tomohiro , Ueda Masataka , Hirose Tomohiko , Otsuka Kazutoshi , Kawasaki Keisuke
Published: April 2023

The accuracy of percutaneous pedicle screw (PSS) placement in the lateral decubitus position has seldom been reported. This study aimed to retrospectively compare the accuracy of PPS placement with 3-dimensional (3D) fluoroscopy-based navigation in 2 cohorts of patients who underwent surgery in the lateral decubitus or prone positions at our single institute. A total of 265 consecutive patients underwent spinal surgery with PPS from T1 (thoracic 1) to S (sacrum) under the 3D fluoroscopy-based navigation system at our institute. Patients were divided into 2 groups based on their intraoperative patient positioning: lateral decubitus (Group L) or prone (Group P). A total of 1816 PPSs were placed from T1 to S, and 76 (4.18%) PPSs were assessed as deviated PPS. Twenty-one of 453 (4.64%) PPSs in Group L deviation and 55 of 1363 (4.04%) PPSs in Group P had deviated PPS, but with not significant difference (P = .580). In Group L, although the PPS deviation rate was not significantly different between the upside and downside PPS, the downside PPS significantly deviated toward the lateral side compared with the upside PPS. The safety and efficacy of PPS insertion in the lateral decubitus position were similar to those in the conventional prone position.
A nonsense mutation in the CUL3 gene in a Chinese patient with autism spectrum disorder and epilepsy: A case report
Authors: Qian Meijia , Lin Shuangzhu , Tan Yangyang , Chen Qiandui , Wang Wanqi , Li Jiayi , Mu Chunyu
Published: April 2023

Rationale:

CUL3 (OMIM: 603136) encodes cullin-3, a core component of ubiquitin E3 ligase. Existing medical research suggests that CUL3 mutations are closely related to neurodevelopmental disorder with or without autism or seizures (neurodevelopmental disorder with autism and seizures, OMIM: 619239). However, the number of published case reports of autism spectrum disorder due to CUL3 gene mutations is limited.

Patient concern:

A four-year-old Chinese girl presented with generalized epilepsy, and then exhibited developmental regression, including loss of her speaking ability, eye contact aversion, and stereotyped behavior.

Diagnoses:

Whole-exome sequencing identified a nonsense mutation in the CUL3 gene, being c.2065A > T (p.Lys689*); no previous similar case was reported. The final diagnosis was autism, epilepsy, and motor growth retardation.

Intervention:

In order to improve quality of life of the patient, she was provided with exercise rehabilitation training and autism behavioral guidance therapy for 3 months.

Outcomes:

The patient’s exercise capacity had improved, and improvements in autism symptoms were not obvious.

Lessons:

For clinicians, patients with developmental regression accompanied with concurrent epilepsy and autism spectrum disorder should be advised that relevant genetic tests are necessary to clarify the diagnosis.
“Who am I?”: Weakened sense of the self in patients with behavioral variant frontotemporal dementia
Authors: El Haj Mohamad , Kapogiannis Dimitrios , Boutoleau-Bretonnière Claire
Published: April 2023

While research has shown a distrusted sense of the self in patients with behavioral variant frontotemporal dementia (bvFTD), little is known about how patients describe their self-image. We used the “Who am I?” task to invite patients with bvFTD and control participants to produce statements beginning with “I am….” We distinguished between statements related to physical, social, and psychological self. Analyses showed fewer statements related to physical, social, and psychological self in the patients with bvFTD than in control participants. Another result was the proportionally similar production of statements describing physical, social, and psychological self in both patients with bvFTD and control participants. Finally, the total production of “Who am I?” statements was positively correlated with verbal fluency in both patients with bvTFD and control participants. Our findings demonstrate a diminished ability of patients with bvFTD to process self-images. Our study also paves the way toward the use of the “Who am I” task as a simple and ecologically valid tool allowing for the quantitative and qualitative assessment of the sense of self in patients with bvFTD.
Progressive muscle relaxation exercises in patients with COVID-19: Systematic review and meta-analysis
Authors: Seid Abubeker Alebachew , Mohammed Ahmed Adem , Hasen Aragaw Asfaw
Published: April 2023

Background:

Patients with COVID-19 will experience high levels of anxiety and depression and poor levels of sleep and quality of life (QoL) due to isolation treatment and uncertain outcomes. Progressive muscle relaxation (PMR) exercises show promising treatment effects on mental health and sleep problems and overall QoL in COVID-19 patients. This study aimed to evaluate the efficacy and safety of PMR exercises in patients with COVID-19.

Methods:

Both experimental and non-experimental studies related to PMR and COVID-19 were systematically searched in the PubMed, Cochrane Library, PEDro and HINARI databases for studies published from the occurrence of the pandemic to December 2022. Study selection, methodological quality assessment and data extraction were carried out by 2 independent authors. Efficacy outcomes were evaluated for sleep quality, anxiety, depression, and QoL. The safety outcomes were evaluated based on adverse events reported. Review manager (RevMan 5.4, Cochrane collaboration) was used for the data analysis.

Results:

Four studies with 227 subjects were included in this systematic review. The pooled results indicated that PMR interventions improved the sleep quality score standardized mean difference (SMD): −0.23; 95% confidence interval (CI): −0.54, 0.07; P = .13, level of anxiety SMD: −1.35; 95% CI −2.38, −0.32; P = .01 compared to the usual care. Depression level, disease severity and QoL were also improved following PMR interventions. Only 1 study reported worsening of 1 patient clinical status while all other studies did not report any adverse events during the interventions.

Conclusions:

PMR interventions can improve the sleep quality, anxiety, depression, disease severity and QoL in patients with mild to moderate COVID-19 in a short-term period compared to the usual care. However, there was indecision about the safety and long-term effects of PMR.
Effects of school sandplay group therapy on children victims of cyberbullying
Authors: Lee Myeong-Bok , Yeom Yeon Ok , Kim Min Sun , Lee Youngil , Kim Kyoung Min , Kim Do Hyun , Lee Chang Min , Lim Myung Ho
Published: April 2023

Cyberbullying among children is increasing every year, leading to serious public health problems. Victims suffer serious aftereffects such as depression and suicidal ideation; therefore, early and appropriate psychological intervention and the role of schools are emphasized. This study investigated the effects of school sandplay group therapy (SSGT) on children affected by cyberbullying. This study was designed as a parallel-group non-randomized controlled trial. The study subjects were 139 elementary school students (mean age 11.35 years; standard deviation, 0.479; age range 12–13 years) residing in Cheonan City, Korea, who were assigned to the intervention and comparison groups. The intervention group received 10 sessions of therapy on a weekly basis, for 40 minutes per session. No therapy was administered in the control group. The effectiveness of the intervention was assessed using the Children Depression Inventory, Suicidal Ideation Questionnaire-Junior, and Rosenberg Self-Esteem Scale. The assessment for the comparison group was performed concurrently with that of the intervention group. Data were analyzed using multivariate analysis of variance. In this study, the SSGT group showed a significant decrease in depression and suicidal ideation compared to the control group after sandplay group therapy (SGT), and a significant increase in self-esteem. It was confirmed that SSGT can mitigate the negative consequences of cyberbullying and strengthen protective factors. This suggests that the SSGT can be successfully used for crisis counseling.
Identification of key genes and immune infiltration based on weighted gene co-expression network analysis in vestibular schwannoma
Authors: Fu Yanpeng , Zhu Yaqiong , Guo Liqing , Liu Yuehui
Published: April 2023

Vestibular schwannomas are the most common tumors of the cerebellopontine angle, but their pathogenesis is still unclear. This study aimed to explore the molecular mechanisms and potential therapeutic target biomarkers in vestibular schwannoma. Two datasets (GSE141801 and GSE54934) were downloaded from the Gene Expression Omnibus database. Weighted gene coexpression network analysis was performed to find the key modules associated with vestibular schwannoma (VS). Functional enrichment analysis was applied to evaluate the gene enrichment signaling pathway in key modules. Protein-protein interaction networks in key modules were constructed using the STRING website. Hub genes were identified by intersecting candidate hub genes in protein-protein interaction network and candidate hub genes in key modules. Single-sample gene set enrichment analysis was utilized to quantify the abundance of tumor-infiltrating immune cells in VSs and normal control nerves. A Random forest classifier was developed based on hub genes identified in this study and validated on an independent dataset (GSE108524). Results of immune cell infiltration were also validated on GSE108524 by gene set enrichment analysis. Eight genes from coexpression modules were identified as hub genes, that is, CCND1, CAV1, GLI1, SOX9, LY86, TLR3, TREM2, and C3AR1, which might be potential therapeutic targets for VS. We also found that there were distinct differences in the infiltration levels of immune cells between VSs and normal control nerves. Overall, our findings may be useful for investigating the mechanisms underlying VS and provide noteworthy directions for future research.
The efficacy and potential mechanism of Danggui Buxue Decoction in treating diabetic nephropathy: A meta-analysis and network pharmacology
Authors: Zhang Yan , Jiang Lijuan , Xue Jiaojiao , Lv Minglong , Zhang Wenfeng
Published: April 2023

Background:

To evaluate the efficacy and potential pharmacological mechanisms of Danggui Buxue Decoction (DGBXD) in the treatment of diabetic nephropathy.

Methods:

Meta-analysis was used to conduct a comprehensive search of the literature for randomized controlled trials of DGBXD for diabetic nephropathy, followed by identification of quantitative literature based on inclusion and exclusion criteria, and statistical analysis of the included data using Review Manager. The network pharmacology technique was used to screen the chemical components of DGBXD and their targets, disease targets, shared targets, and other associated information, and then apply bioinformatics technologies to annotate the key pathways. Using AutoDock and PyMol software, the 6 core targets were docked with the 7 main active components of DGBXD.

Results:

DGBXD complementary treatment significantly reduced 24 hours UTP, SCr and BUN levels and lowered blood glucose and lipid levels, improving clinical outcomes and modulating inflammatory factor levels. 22 active ingredients and 209 active targets were obtained for DGBXD, 245 core targets were obtained for diabetic nephropathy. The molecular docking results showed that all 7 components of DGBXD docked with 6 core targets had binding energies below −5.

Conclusions:

The findings suggest that DGBXD affects diabetic nephropathy through a multi-target, multi-component and multi-pathway mechanism.
Identification of key genes and potential mechanisms based on the autophagy regulatory network in intervertebral disc degeneration
Authors: Lv Chang , Chen Kai , Zhu Lixin
Published: April 2023

Intervertebral disc degeneration (IDD) is a common musculoskeletal disease that develops with increasing age. However, the exact occurrence and progression of IDD remains unclear. Gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) repository. The NCBI GEO2R analysis tool was used to identify differentially expressed genes. The protein-protein interaction (PPI) network was predicted using the STRING website and visualized using the Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to enrich GO terms and signaling pathways using the Metascape database. To identify potential upstream miRNA targets of these differentially expressed genes, the mRNA-miRNA interaction networks were predicted by Network Analyst database. To identify the 2 key genes with significant differences among the 10 hub genes, the GraphPad Prism Tool and GeneCards database were used for analysis. 22 genes were identified. A PPI network was constructed and the other 30 related genes were deduced. GO and Kyoto Encyclopedia of Genes and Genomes enrichment networks indicated extracellular matrix organization, collagen-containing extracellular matrix and extracellular matrix structural constituent in extracellular matrix (ECM) regulation in IDD. The mRNA-miRNA interaction networks suggested that many miRNAs could regulate autophagy-related genes individually and collectively. The GraphPad Prism Tool and GeneCards database analysis results suggested that 2 hub genes were involved in IDD. Our results revealed that the role of ECM could be a regulatory mechanism in IDD and that these ECM-related genes might be targets for the intervention of IDD.
Ultrasonic diagnosis of delayed hematoma during emergency removal of traumatic intracranial hematoma: A case report and literature review
Authors: Weng Yan , Shang Ziqi , Zhong Qing
Published: April 2023

Rationale:

It is emergency and vital during neurosurgical procedure in traumatic intracranial when an acute intraoperative brain bulge (AIBB) is occurred. It is important to get a diagnosis quickly.

Patient concerns:

A 44-year-old man was undergone a neurosurgical procedure for the left side of traumatic intracranial hematoma. An AIBB was occurred during the surgery. Computed tomography (CT) is always used in diagnosis when an AIBB is occurred, but more time is needed when CT is conducted.

Diagnoses:

We diagnosed the AIBB through bedside real-time ultrasound, and a delayed hematoma which caused the AIBB was found.

Interventions:

A further neurosurgical procedure of right intracranial hematoma was performed for the patient.

Outcomes:

The surgical effect and the patient’s prognosis were significantly improved.

Lessons:

Through this patient, we should pay more attention to the application of perioperative of real-time ultrasonic monitoring, to provide more convenience for surgical patients, and improve the prognosis of them.
Impact of the COVID-19 pandemic on the psychological status of undergraduate medical students in Saudi Arabia: A cross-sectional double-scale study
Authors: Ewid Mohammed , Amal Yassien , Billah Syed Muhammad Baqui , Kalou Yazan , Zitoun Osama A. , Alnaser Adnan Raed , Nashawi Mhd Oubai , Almazrou Abdulrahman
Published: April 2023

The COVID-19 pandemic is a major health care catastrophe that affects people’s physical and mental well-being worldwide. Medical students are at an increased risk of mental health hazards during the COVID-19 pandemic. Sulaiman Al Rajhi University (SRU), the site of our study, is located in Qassim province in the Kingdom of Saudi Arabia. We conducted this study to assess the prevalence of depression, stress and anxiety symptoms among SRU medical students during the quarantine and while learning online shortly after the announcement of documented COVID-19 cases in Kingdom of Saudi Arabia. In this cross-sectional study, an online questionnaire was sent to all medical students of SRU; 278 students responded (71%). We collected participants’ demographic, socioeconomic, and academic data. The Depression, Anxiety, and Stress scale and the Fear of COVID-19 Scale were used as the validated mental health assessment tools. Depression, anxiety and stress symptoms were found in 23%, 11%, and 6% of students, respectively. Females were more likely to have anxiety (P = .03) than males. Students who had close contact with COVID-19 cases, those whose lives were affected by COVID-19, and those with poor socioeconomic status had significantly higher levels of stress, anxiety, and depression compared to their counterparts (P = .004, .01, .01, respectively). Students from high-viral-load areas, unmarried students, and those who did not live with their families were more stressed (P = .06, .01, .01, respectively). The Fear of COVID-19 Scale was positively correlated with all Depression, Anxiety, and Stress components (depression: r = 0.36, anxiety: r = 0.45, and stress: r = 0.39, P < .001 for all). Medical students, especially female students, are at an increased risk of developing depression, anxiety, and stress symptoms with increased COVID-19 fear during the pandemic. The study highlights the importance of mental health screening for female students, students of low socioeconomic status, and relatives of COVID-19 cases. Our findings could help institutions adjust mental health services in the future amid such pandemics.
Study on acupuncture improving sleep deprivation comorbid with cognitive dysfunction based on rs-fMRI: A protocol for systematic review and meta-analysis
Authors: Guo Xiaole , Yang Weiwan , Wang Ying , Ma Shiqi , Lu Qi , Wang Hongfeng
Published: April 2023

Background:

Sleep deprivation often lead to changes in attention, memory, mood, alertness, and metabolism. Especially, it is often accompanied by cognitive impairment of the brain. Acupuncture is safe and effective for improving cognitive function, but its underlying mechanism is not fully understood. Resting-state functional magnetic resonance imaging is an important means to study brain activity changes. However, the results are inconsistent and lack systematic evaluation and analysis.

Methods:

We will search 9 databases, including PubMed, EMBASE, EBSCOhost-Medline, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP Database and Wan-Fang Database, Chinese Biomedical Literature Database, and 2 clinical trials register platforms: Chinese Clinical Trial Registry, ClinicalTrials.gov (www.ClinicalTrials.gov/) from inception to November 1, 2022. We will use the Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures.

Results:

This study will analyze the effect of acupuncture on brain activity changes, improvement of sleep duration, and cognitive impairment.

Conclusion:

This meta-analysis aims to investigate the efficacy of acupuncture on brain activity changes in sleep deprivation comorbid with cognitive dysfunction, so as to provide effective evidence for clarifying its pathogenesis.
Association of osteoporosis risk and polymorphisms of osteoprotegerin gene T950C in postmenopausal Chinese women: A PRISMA-compliant meta-analysis
Authors: Xia Yuansheng , Chen Huiyan
Published: April 2023

Background:

This study aimed to assess the association between the T950C polymorphism and osteoporosis in postmenopausal Chinese women to further reduce the influence of different genetic backgrounds by meta-analysis and subgroup analysis.

Methods:

Through November 2022, a systematic online investigation was performed with the aid of the Cochrane Library, EMBASE, PubMed, Web of Science and the Chinese National Knowledge Infrastructure to find case-control studies looking into the correlation between the osteoprotegerin gene (OPG) T950C polymorphism and postmenopausal osteoporosis susceptibility.

Results:

This study included 6 studies with a total of 1669 postmenopausal osteoporosis cases and 2992 controls. In the recessive model, postmenopausal women with the CC genotype (mutant homozygote at the T950C locus) had a lower risk of osteoporosis, indicating that the CC genotype of OPG T950C might show a preventive effect on osteoporosis after menopause. In a stratified analysis by geographic area, the population from South China had a significantly higher risk under the dominant model [CC + TC (heterozygote at the T950C locus) vs TT (wild-type homozygotes at the T950C locus): odds ratio = 1.34, 95% confidence interval = 1.17–1.54, P < .01], while the population from South China had a significantly lower risk under the recessive model (CC vs TC + TT: odds ratio = 0.79, 95% confidence interval = 0.69–0.95, P = .02).

Conclusions:

Together, the OPG T950C polymorphism may be associated with osteoporosis risk in postmenopausal Chinese women, according to this meta-analysis. Because of the study’s limitations, more large-scale research is needed to corroborate these findings.
Pediatric Intestinal Pseudo-Obstruction: An International Survey on Diagnostic and Management Strategies in the European Reference Network for Rare Inherited and Congenital Anomalies Intestinal Failure Teams
Authors: Mutanen Annika , Demirok Aysenur , Wessel Lucas , Tabbers Merit ,   on behalf of ERNICA IF Working Group
Published: April 2023

Objectives:

Pediatric intestinal pseudo-obstruction (PIPO) management is based on nutritional, medical, and surgical care while available evidence is scarce. The aim of this study was to outline the current diagnostic and management strategies in intestinal failure (IF) teams of the European Reference Network for rare Inherited and Congenital Anomalies (ERNICA) and to compare these practices to the latest PIPO international guidelines.

Methods:

An online survey on institutional diagnostic and management strategies of PIPO was conducted among the ERNICA IF teams.

Results:

In total, 11 of 21 ERNICA IF centers from 8 countries participated. On average, 64% of teams had ≥6 and 36% had 1–5 PIPO patients under active follow-up. In total, 80 of 102 PIPO patients were parenteral nutrition (PN) dependent while each IF team had median 4 (range 0–19) PN dependent PIPO patients under follow-up. On average, each center received 1–2 new PIPO patients per year. Diagnostics mostly followed current guidelines while medical and surgical management strategies were diverse.

Conclusions:

Numbers of PIPO patients are low and management strategies are diverse among ERNICA IF teams. To improve PIPO patient care, regional reference centers with specialized multidisciplinary IF teams and continuous collaboration across centers are needed.