bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells
Authors: Mulcahy Victoria , Liaskou Evaggelia , Martin Jose-Ezequiel , Kotagiri Prasanti , Badrock Jonathan , Jones Rebecca L. , Rushbrook Simon M , Ryder Stephen D. , Thorburn Douglas , Taylor-Robinson Simon D. , Clark Graeme , Cordell Heather J. , Sandford Richard N. , Jones David E. , Hirschfield Gideon M. , Mells George F. 
Published: April 2023

Background & Aims:
In patients with primary biliary cholangitis (PBC), the serum liver biochemistry measured during treatment with ursodeoxycholic acid—the UDCA response—accurately predicts long-term outcome. Molecular characterization of patients stratified by UDCA response can improve biological understanding of the high-risk disease, thereby helping to identify alternative approaches to disease-modifying therapy. In this study, we sought to characterize the immunobiology of the UDCA response using transcriptional profiling of peripheral blood mononuclear cell subsets.

Methods:
We performed bulk RNA-sequencing of monocytes and TH1, TH17, TREG, and B cells isolated from the peripheral blood of 15 PBC patients with adequate UDCA response (“responders”), 16 PBC patients with inadequate UDCA response (“nonresponders”), and 15 matched controls. We used the Weighted Gene Co-expression Network Analysis to identify networks of co-expressed genes (“modules”) associated with response status and the most highly connected genes (“hub genes”) within them. Finally, we performed a Multi-Omics Factor Analysis of the Weighted Gene Co-expression Network Analysis modules to identify the principal axes of biological variation (“latent factors”) across all peripheral blood mononuclear cell subsets.

Results:
Using the Weighted Gene Co-expression Network Analysis, we identified modules associated with response and/or disease status (q<0.05) in each peripheral blood mononuclear cell subset. Hub genes and functional annotations suggested that monocytes are proinflammatory in nonresponders, but antiinflammatory in responders; TH1 and TH17 cells are activated in all PBC cases but better regulated in responders; and TREG cells are activated—but also kept in check—in responders. Using the Multi-Omics Factor Analysis, we found that antiinflammatory activity in monocytes, regulation of TH1 cells, and activation of TREG cells are interrelated and more prominent in responders.

Conclusions:
We provide evidence that adaptive immune responses are better regulated in patients with PBC with adequate UDCA response.
Photobiomodulation therapy for large soft drusen and drusenoid pigment epithelial detachment in age-related macular degeneration: a single-center prospective pilot study
Authors: Benlahbib Manal , Cohen Salomon Yves , Torrell Nuria , Colantuono Donato , Crincoli Emanuele , Amoroso Francesca , Semoun Oudy , Jung Camille , Souied Eric H 
Published: April 2023

Abstract

Purpose:
To evaluate visual acuity and morphologic changes after photobiomodulation (PBM) for patients affected with large soft drusen and/or drusenoid pigment epithelial detachment (dPED) associated to dry age-related macular degeneration (AMD).

Method:
Twenty eyes with large soft drusen and/or dPED AMD were included and treated with the LumiThera® ValedaTM Light Delivery System. All subjects underwent 2 treatments per week for 5 weeks. Outcome measures included best corrected visual acuity (BCVA), microperimetry- scotopic testing, drusen volume (DV), central drusen thickness (CDT), quality of life (QoL) score at baseline and month 6 (M6) follow up. Data of BCVA, DV and CDT was also recorded at week 5 (W5).

Results:
BCVA significantly improved at M6 with a mean score gain of 5.5 letters (p = 0.007). Retinal sensitivity (RS) decreased by 0.1 dB (p=0.17). Mean fixation stability increased by 0.45 % (P=0.72). DV decreased by 0.11 mm3 (p=0.03). CDT was reduced by a mean of 17.05 µm (p=0.01). GA area increased by 0.06 mm2 (p=0.01) over a 6 months follow up, quality of life score increased by 3,07 points on average (p=0.05). One patient presented a dPED rupture at M6 after PBM treatment.

Conclusion:
The visual and anatomical improvements in our patients support previous reports on PBM. PBM may provide a valid therapeutic option for large soft drusen and dPED AMD and may potentially slow the natural course of the disease.
Traditional Chinese medicine regulates inflammatory factors in chronic prostatitis/chronic pelvic pain syndrome: A review
Authors: Wang Hao , Zhao Ming , Zhang Jiwei , Yan Bin , Gao Qinghe , Guo Jun 
Published: April 2023

ABSTRACT
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease, and its clinical manifestations are closely related to the dysregulation of inflammatory factors. Nonsteroidal anti-inflammatory drugs have been shown to be effective in managing inflammation and providing pain relief, but their clinical application remains controversial. Traditional Chinese medicine (TCM) is widely used to regulate inflammatory factors in CP/CPPS, and treatment with TCM has gained some advantages based on an “individualized” or “personalized” medical approach. In addition, TCM extracts and acupuncture therapy have also been proven to be effective for CP/CPPS, as they regulate related inflammatory factors. However, current systematic reviews tend to verify the efficacy and safety of TCM therapies in CP/CPPS, and there is still a deficiency in sorting out their mechanisms of modulating inflammatory factors. Based on the current evidence, our review summarizes the application of TCM in regulating inflammatory factors in CP/CPPS to provide a reference for the treatment of CP/CPPS with TCM therapy and a potential direction with future studies in this field.
The invisible cost of pain management by the current International Classification of Diseases coding system: a study in a tertiary care inpatient setting
Authors: Eiamtanasate Sarasate , Smithiseth Kannika , Zinboonyahgoon Nantthasorn , Korwisi Beatrice , Barke Antonia , Rief Winfried , Treede Rolf-Detlef 
Published: April 2023

Abstract
The International Classification of Diseases (ICD) is applied worldwide for public health data collection among other use cases. However, the current version of the ICD (ICD-10), to which the reimbursement system is linked in many countries, does not represent chronic pain properly. This study aims to compare the ICD-10 with the ICD-11 in hospitalized patients in terms of specificity, clinical utility, and reimbursement for pain management. The medical records of hospitalized patients consulted for pain management at Siriraj Hospital, Thailand, were reviewed, and all pain-related diagnoses were coded into ICD-10 and ICD-11. The data of 397 patients showed unspecified pain was coded 78% in the ICD-10 and only 0.5% in the ICD-11 version. The difference gap in the proportion of unspecified pain between the 2 versions is wider than in the outpatient setting. The 3 most common codes for ICD-10 were other chronic pain, low back pain, and pain in limb. The 3 most common codes for ICD-11 were chronic cancer pain, chronic peripheral neuropathic pain, and chronic secondary musculoskeletal pain. As in many other countries, no pain-related ICD-10 codes were coded for routine reimbursement. The simulated reimbursement fee remained the same when adding 397 pain-related codings, even if the cost of pain management, such as cost of labor, existed. Compared with the ICD-10 version, the ICD-11 is more specific and makes pain diagnoses more visible. Thus, shifting from ICD-10 to ICD-11 has the potential to improve both the quality of care and the reimbursement for pain management.
Vaporized cannabis extract–induced antinociception in male vs female rats with persistent inflammatory pain
Authors: Craft Rebecca M. , Gogulski Hannah Y. , Freels Timothy G. , Glodosky Nicholas C. , McLaughlin Ryan J. 
Published: April 2023

AbstractAlthough preclinical studies generally report robust antinociceptive effects of cannabinoids in rodent persistent pain models, randomized controlled trials in chronic pain patients report limited pain relief from cannabis/cannabinoids. Differences between animal and human studies that may contribute to these discrepant findings include route of cannabis/cannabinoid administration, type of cannabis/cannabinoid, and how pain is measured. To address these factors, rats with complete Freund adjuvant (CFA)–induced hind paw inflammation were exposed acutely or repeatedly to vaporized cannabis extract that was either tetrahydrocannabinol (THC) or cannabidiol (CBD)dominant. One measure of evoked pain (mechanical threshold), 2 functional measures of pain (hind paw weight-bearing, and locomotor activity), and hind paw edema were assessed for up to 2 hours after vapor exposure. Acute exposure to vaporized THC-dominant extract (200 or 400 mg/mL) decreased mechanical allodynia and hind paw edema and increased hind paw weight-bearing and locomotor activity, with no sex differences. After repeated exposure to vaporized THC-dominant extract (twice daily for 3 days), only the antiallodynic effect was significant. Acute exposure to vaporized CBD-dominant cannabis extract (200 mg/mL) did not produce any effects in either sex; repeated exposure to this extract (100, 200, or 400 mg/mL) decreased mechanical allodynia in male rats only. Sex differences (or lack thereof) in the effects of vaporized cannabis extracts were not explained by sex differences in plasma levels of THC, CBD, or their major metabolites. These results suggest that although vaporized THC-dominant extract is likely to be modestly effective against inflammatory pain in both male and female rats, tolerance may develop, and the CBD-dominant extract may be effective only in male rats.
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.
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.
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.