bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring causal structures of gut microbiota diversity and feed efficiency traits in poultry using Bayesian learning and genomic structural equation models
Authors: Haas Valentin , Rodehutscord Markus , Camarinha-Silva Amélia , Bennewitz Jörn
Published: February 2023

Feed and phosphorus (P) efficiency are of increasing importance in poultry breeding. It has been shown recently that these efficiency traits are influenced by the gut microbiota composition of the birds. The efficiency traits and the gut microbiota composition are partly under control of the host genome. Thus, the gut microbiota composition can be seen as a mediator trait between the host genome and the efficiency traits. The present study used data from 749 individuals of a Japanese quail F2 cross. The birds were genotyped for 4k single-nucleotide polymorphism (SNP) and trait recorded for P utilization (PU) and P retention (PR), body weight gain (BWG), and feed per gain ratio (F:G). The gut microbiota composition was characterized by targeted amplicon sequencing. The alpha diversity was calculated as the Pielou’s evenness index (Jʹ). A stable Bayesian network was established using a Hill-Climbing learning algorithm. Pielou’s evenness index was placed as the most upstream trait and BWG as the most downstream trait, with direct and indirect links via PR, PU, and F:G. The direct and indirect effects between Jʹ, PU, and PR were quantified with structural equation models (SEM), which revealed a causal link from Jʹ to PU and from PU to PR. Quantitative trait loci (QTL) linkage mapping revealed three genome-wide significant QTL regions for these traits with in total 49 trait-associated SNP within the QTL regions. SEM association mapping separated the total SNP effect for a trait into a direct effect and indirect effects mediated by upstream traits. Although the indirect effects were in general small, they contributed to the total SNP effect in some cases. This enabled us to detect some shared genetic effects. The method applied allows for the detection of shared genetic architecture of quantitative traits and microbiota compositions.
A comparison of the baryonic Tully–Fisher relation in MaNGA and IllustrisTNG
Authors: Goddy Julian S , Stark David V , Masters Karen L , Bundy Kevin , Drory Niv , Law David R
Published: February 2023

We compare an observed baryonic Tully–Fisher relation (BTFR) from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) and HI-MaNGA surveys to a simulated BTFR from the cosmological magnetohydrodynamical simulation, IllustrisTNG. To do so, we calibrate the BTFR of the local universe using 377 galaxies from the MaNGA and HI-MaNGA surveys, and perform mock 21 cm observations of matching galaxies from IllustrisTNG. The mock observations are used to ensure that the comparison with the observed galaxies is fair since it has identical measurement algorithms, observational limitations, biases, and uncertainties. For comparison, we also calculate the BTFR for the simulation without mock observations and demonstrate how mock observations are necessary to fairly and consistently compare between observational and theoretical data. We report a MaNGA BTFR of log$_{10} (M_{ \rm Bary}/M_\odot)= (2.97 \pm 0.18)$ log$_{10} V_{ \rm Rot} + (4.04 \pm 0.41)\, \log _{10}{M_{\odot }}$ and an IllustrisTNG BTFR of log$_{10} (M_{ \rm Bary}/M_\odot) = (2.94 \pm 0.23$) log$_{10} V_{ \rm Rot} + (4.15 \pm 0.44)\, \log _{10}{M_{\odot }}$. Thus, MaNGA and IllustrisTNG produce BTFRs that agree within uncertainties, demonstrating that IllustrisTNG has created a galaxy population that obeys the observed relationship between mass and rotation velocity in the observed universe.
Testis-specific actin-like 7A (ACTL7A) is an indispensable protein for subacrosomal-associated F-actin formation, acrosomal anchoring, and male fertility
Authors: Ferrer P , Upadhyay S , Ikawa M , Clement T M
Published: February 2023

Formation of the acrosome during spermiogenesis is an essential process for creating fertilization-competent sperm. Of the numerous aspects required for acrosome biogenesis, adherence of the acrosomal outer membrane to the nuclear surface is mediated by the subacrosomal perinuclear theca. However, the cellular dynamics and congruent functions pertaining to these acrosomal anchoring factors are not well understood despite many of them being implicated as potential causes for human male infertility. Actin-like 7A (ACTL7A) is one such factor for which deleterious polymorphisms have recently been shown to cause human male infertility. It is thought that acrosomal attachment is coordinated by cytoskeletal associations between the acrosome and nucleus via the acroplaxome. To further illuminate the mechanistic underpinnings of ACTL7A for essential acrosome associations, in this study, we investigated its dynamic localization in the developing germline, molecular associations with other cytoskeletal components, and the cellular consequences of ablation. Our intracellular localization data show ACTL7A to be dynamically present within the nucleus and subacrosomal space and later associated with postacrosomal regions of developing spermatids. Through the generation of an Actl7a knock-out mouse model, we consistently observed disruption of acrosomal biogenesis with abnormal migration of the acrosomal granule and peeling acrosomes during spermatid elongation. Significantly, we found a complete loss of subacrosomal filamentous actin (F-actin) structures in knock-out spermatids suggesting a regulatory role for subacrosomal F-actin. Considering our reported data together with existing literature, we propose a mechanistic model explaining the essential role of ACTL7A for acroplaxome-associated F-actin, acrosomal attachment integrity, and male fertility.
MALDI mass spectrometry imaging shows a gradual change in the proteome landscape during mouse ovarian folliculogenesis
Authors: Fiorentino Giulia , Smith Andrew , Nicora Giovanna , Bellazzi Riccardo , Magni Fulvio , Garagna Silvia , Zuccotti Maurizio
Published: February 2023

Our knowledge regarding the role proteins play in the mutual relationship among oocytes, surrounding follicle cells, stroma, and the vascular network inside the ovary is still poor and obtaining insights into this context would significantly aid our understanding of folliculogenesis. Here, we describe a spatial proteomics approach to characterize the proteome of individual follicles at different growth stages in a whole prepubertal 25-day-old mouse ovary. A total of 401 proteins were identified by nano-scale liquid chromatography–electrospray ionization–tandem mass spectrometry (nLC-ESI-MS/MS), 69 with a known function in ovary biology, as demonstrated by earlier proteomics studies. Enrichment analysis highlighted significant KEGG and Reactome pathways, with apoptosis, developmental biology, PI3K-Akt, epigenetic regulation of gene expression, and extracellular matrix organization being well represented. Then, correlating these data with the spatial information provided by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) on 276 follicles enabled the protein profiles of single follicle types to be mapped within their native context, highlighting 94 proteins that were detected throughout the secondary to the pre-ovulatory transition. Statistical analyses identified a group of 37 proteins that showed a gradual quantitative change during follicle differentiation, comprising 10 with a known role in follicle growth (NUMA1, TPM2), oocyte germinal vesicle-to-metaphase II transition (SFPQ, ACTBL, MARCS, NUCL), ovulation (GELS, CO1A2), and preimplantation development (TIF1B, KHDC3). The proteome landscape identified includes molecules of known function in the ovary, but also those whose specific role is emerging. Altogether, this work demonstrates the utility of performing spatial proteomics in the context of the ovary and offers sound bases for more in-depth investigations that aim to further unravel its spatial proteome.
Materiality of Sonic Imagery: On Analysis of Contemporary Chinese Compositions
Authors: Rao Nancy Yunhwa
Published: February 2023

This essay explores concepts related to the materiality of sound and considers the aesthetics of contemporary Chinese music (and of other Asian heritages) through this lens. In compositions such as Guo Wenjing’s chamber work She Huo, musical expression is prominently shaped by sonic ideas rooted in socio-historical and cultural contexts, and associated with materials of substance and matter. Analysis of such works requires reconceptualizing the modes of analysis and listening practice. Through a focus on materiality, I argue, we gain insight about the music in ways unattainable from established, ingrained modes of musical analysis. Examples explored include the significance of onomatopoeic words for the notation of percussion music in Peking opera; the concept of sawari in Japanese instrumental music, as discussed by Tōru Takemitsu; and Isang Yun’s notion of Hauptton. Music’s materiality comprises many dimensions, the consideration of which is of great importance as we seek to broaden the canon.
Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis
Authors: Haschka Judith , Simon David , Bayat Sara , Messner Zora , Kampylafka Eleni , Fagni Filippo , Skalicky Susanna , Hackl Matthias , Resch Heinrich , Zwerina Jochen , Kleyer Arnd , Cavallaro Alexander , Sticherling Michael , Schett Goerg , Kocijan Roland , Rech Juergen
Published: February 2023

Objective

miRNAs are small non-coding RNAs that control gene expression. Specific intra- and extracellular miRNA signatures have been identified in various diseases. Whether certain miRNA signatures are associated with psoriasis (PsO) and PsA is currently unknown. We aimed to search for circulating miRNA signatures associated with PsO and PsA patients.

Methods

Expression of miRNAs was analysed by reverse transcription quantitative real-time PCR (RT-qPCR) in the serum of PsA, PsO patients and healthy controls. Demographic and disease-specific characteristics and imaging data from hand MRI were recorded. In the discovery phase, 192 miRNA assays were analysed in 48 samples (PsA, PsO, controls: each N = 16). For validation, 17 selected miRNAs were measured in the total population.

Results

A total of 141 patients and controls were analysed (51 PsA, 40 PsO, 50 controls). In the discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared with controls, with 33 miRNAs being changed in both (adj. P < 0.05). The 17 top candidates from discovery were assessed in the validation phase, 9 of them discriminated PsA and PsO from controls [area under the curve (AUC) ≥0.70, all P < 0.05]. Four miRNAs (miR-19b-3p, miR-21-5p, miR-92a-3p and let-7b-5p) were significantly differently regulated between PsO and PsA. A combination of these miRNAs increased the AUC to 0.92 in multivariate regression model to discriminate PsO and PsA.

Conclusion

miRNA signatures in PsA and PsO patients differ from controls. Nine miRNAs were differentially regulated in PsA and PsO patients, five of them previously reported to be involved in bone and cartilage metabolism, indicating an intimate association of psoriatic inflammation and bone/cartilage changes.
Diagnostic Delays in Sepsis: Lessons Learned From a Retrospective Study of Canadian Medico-Legal Claims
Authors: Neilson Heather K. , Fortier Jacqueline H. , Finestone PJ. , Ogilby Catherine M. , Liu Richard , Bridges Eileen J. , Garber Gary E.
Published: February 2023

IMPORTANCE:

Although rapid treatment improves outcomes for patients presenting with sepsis, early detection can be difficult, especially in otherwise healthy adults.

OBJECTIVES:

Using medico-legal data, we aimed to identify areas of focus to assist with early recognition of sepsis.

DESIGN, SETTING, AND PARTICIPANTS:

Retrospective descriptive design. We analyzed closed medico-legal cases involving physicians from a national database repository at the Canadian Medical Protective Association. The study included cases closed between 2011 and 2020 that had documented peer expert criticism of a diagnostic issue related to sepsis or relevant infections.

MAIN OUTCOMES AND MEASURES:

We used univariate statistics to describe patients and physicians and applied published frameworks to classify contributing factors (provider, team, system) and diagnostic pitfalls based on peer expert criticisms.

RESULTS:

Of 162 involved patients, the median age was 53 years (interquartile range [IQR], 34–66 yr) and mortality was 49%. Of 218 implicated physicians, 169 (78%) were from family medicine, emergency medicine, or surgical specialties. Eighty patients (49%) made multiple visits to outpatient care leading up to sepsis recognition/hospitalization (median = two visits; IQR, 2–4). Almost 40% of patients were admitted to the ICU. Deficient assessments, such as failing to consider sepsis or not reassessing the patient prior to discharge, contributed to the majority of cases (81%).

CONCLUSIONS AND RELEVANCE:

Sepsis continues to be a challenging diagnosis for clinicians. Multiple visits to outpatient care may be an early warning sign requiring vigilance in the patient assessment.
Impact of Extended Adjuvant Temozolamide Beyond 6 Months in the Management of Glioblastoma Patients
Authors: Elsaka Rasha , Kitagwa Joan Minyika , Refaat Tamer , Mahmoud Amr A. , Shaikh Hamza , Meheissen Mohamed A.M. , Elsaid Amr Abdelaziz
Published: February 2023

Objectives:

Our study aimed to assess the benefit of prolonging adjuvant temozolomide (TMZ) therapy beyond 6 cycles in glioblastoma multiform patients.

Materials and Methods:

The medical records of 329 patients in 2 cancer centers in Egypt were reviewed from January 2008 to December 2018 who were diagnosed with diffuse gliomas. Data were collected on patient demographics, presenting complaints, tumor size, treatment modalities (extent of surgery, radiotherapy dose and technique, concomitant TMZ, and the number of adjuvant TMZ cycles), and reported adverse events.

Results:

In the studied cohort, 105 patients were treated with adjuvant TMZ, 33 patients received <6 cycles (TMZL), 41 patients received the standard 6 cycles (TMZS), and 31 patients received >6 cycles (TMZE). Our results showed the median overall survival in the TMZL arm was 8.47 months compared with 15.83 months in the TMZS arm and 27.33 months in the TMZE arm (P < 0.001). Furthermore, a median progression-free survival of 6.35 months was reported in the TMZL group versus, 12.7 and 22.90 months in (TMZS) and (TMZE) groups, respectively(P < 0.001). In the multivariate analysis, the extended adjuvant TMZ with a hazard ratio of 3.106 (95% CI: 2.43-14.46; P < 0.001) was statistically significantly associated with a better outcome.

Conclusions:

Extended adjuvant TMZ therapy beyond 6 cycles may significantly improve the progression-free survival and overall survival in patients with glioblastoma multiform.
Validation of the Chinese Versions of the Carolina Human Papillomavirus (HPV) Immunization Attitudes and Beliefs Scale and HPV and Vaccination Knowledge Scales
Authors: Lo Suzanne Hoi Shan , Chau Janita Pak Chun , Butt Laveeza , Choi Kai Chow
Published: February 2023

Background:

It is vital to address parents’ human papillomavirus (HPV) knowledge, attitudes, and beliefs to reduce vaccine hesitancy and increase adolescent HPV vaccination rates.

Objective:

To validate the Chinese versions of the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS), HPV Knowledge scale (GK23), and Vaccination Knowledge Scale (VK9) and to investigate parents’ current perspectives on HPV vaccination.

Methods:

Convenience sampling was used to recruit 195 Chinese parents. The CHIAS, GK23, and VK9 were translated into Chinese and content validity was established. The structural validity of the CHIAS was assessed by confirmatory factor analysis, and internal consistency of the scales was assessed by Cronbach’s alpha (α) for the CHIAS-C and by Kuder-Richardson 20 for the GK23 and VK9.

Results:

Internal consistency of all 3 scales was acceptable, with Cronbach’s α for the 4 domains of the CHIAS-C ranging from 0.68 to 0.85, and Kuder-Richardson 20 score of 0.88 and 0.75 for the GK23 and VK9, respectively. The 4-factor structure of the CHIAS-C was found to be a good fit to the data and its structural validity was established.

Conclusions:

The Chinese versions of the CHIAS, GK23, and VK9 are valid and reliable instruments to evaluate attitudes, beliefs, and knowledge of HPV and HPV vaccination among Chinese-speaking parents.

Implications for Practice:

These instruments may facilitate investigation of parents’ views toward HPV vaccination and inform the design of targeted interventions to address vaccine hesitancy.

What Is Foundational:

Parents’ knowledge and attitudes are determining factors in vaccination decision-making and should be considered in HPV vaccine promotion efforts.
Phenol–Croton Oil Chemical Peeling Induces Durable Improvement of Constitutional Periorbital Dark Circles
Authors: Soon Seaver L. , Wambier Carlos G. , Rullan Peter R. , Sterling J. Bart , Brody Harold J. , Lee Kachiu C. , Kreyden Oliver P. , Landau Marina
Published: February 2023

BACKGROUND

Constitutional periorbital dark circles (PDC) are common in skin of color and represent a therapeutic challenge.

OBJECTIVE

To summarize the experience of the International Peeling Society on the safety and effectiveness of deep chemical peeling in the treatment of constitutional PDC.

MATERIALS AND METHODS

Multi-institutional, retrospective case series (1990–2020) of constitutional PDC treated by deep chemical peeling. Descriptive analysis by age, sex, Fitzpatrick phototype, phenol–croton formula, degree and durability of improvement, and complications.

RESULTS

Fifty-five phenol–croton oil peels were performed in 52 patients: 3 patients received a second peel for periorbital rhytids 72 to 84 months after the first peel. 92% (48/52) of patients were women; the median age was 46 years (range, 23–68 years). 89% (46/52) of patients were Fitzpatrick III-IV. Most common formula included phenol 60% to 65% and croton oil 0.6% to 0.7%. 89% (49/55) of peels demonstrated >50% clinical improvement. The median duration of improvement was 24 months (range, 1.5–168 months), and 69% (36/52) of patients demonstrated ongoing improvement at the last follow-up. 4% (2/55) of peels exhibited complications of persistent erythema that resolved without scarring.

CONCLUSION

Based on its safety and effectiveness, deep chemical peels are a treatment of choice for constitutional PDC.
Principles of Care for Patients with Craniofacial Ballistic Injuries
Authors: Yu Jack , Tidwell Taylor , Schaefer Amanda , Lin Kant , Lee Chia-Chun , Wang Tien-Hsiang
Published: February 2023

The mortality rate from firearm injuries in the US has decreased from 30.3 per 100,000 people in 1990 to 20.6 in 2010, likely due to improvement in treatments. However, the incidence of gunshot wounds continues to increase, including the number of mass shootings, even though the definition of which is still unclear. According to Gun Violence Archives (GVA) there were 346 mass shootings in the US, defined as 4 or more injuries in a single incident, in 2017, with 437 deaths and 1803 injured. This article briefly reviews the ballistics of firearms pertinent for maxillofacial surgeons and summarizes the lessons learned from caring for patients with ballistic injuries to the craniofacial region based on the available peer-reviewed publications and the authors’ combined experience of more than six decades. Specifically, we discuss in details the roles of plastic surgeons as a member of the multidisciplinary trauma team in the following three phases: damage control, definitive treatment, long-term rehabilitation.
OMEGA-3 FATTY ACIDS ARE ASSOCIATED WITH DECREASED PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY
Authors: Weir Natalie L. , Guan Weihua , Karger Amy B. , Klein Barbara E. K. , Meuer Stacy M. , Cotch Mary Frances , Guo Xiuqing , Li Xiaohui , Tan Jingyi , Genter Pauline , Chen Yii-Der Ida , Rotter Jerome I. , Ipp Eli , Tsai Michael Y.
Published: February 2023

Purpose:

Inflammation is associated with diabetic retinopathy development and progression, and previous studies have demonstrated that omega-3 polyunsaturated fatty acids have anti-inflammatory properties. Therefore, the goal of this study was to determine if omega-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are associated with decreased risk and severity of retinopathy in individuals with type 2 diabetes.

Methods:

In a combined population of 1,356 individuals with type 2 diabetes from the Multi-Ethnic Study of Atherosclerosis and Genetics of Latino Diabetic Retinopathy cohorts, odds ratios using logistic regression were determined to assess the association between polyunsaturated fatty acids and retinopathy.

Results:

In 1,356 participants with type 2 diabetes, individuals in the fourth quartile of DHA were 17% less likely to have retinopathy compared with the first quartile (P = 0.009, CI: 0.72–0.95). Secondary analysis revealed 38% lower severity of retinopathy in individuals in the fourth quartile compared with the first quartile of DHA (P = 0.006; CI: 0.44–0.87) and EPA + DHA (P = 0.004; CI: 0.44–0.85). No significant associations were observed between EPA and retinopathy.

Conclusion:

DHA is inversely associated with the presence and severity of diabetic retinopathy. Increased intake of dietary sources of DHA may provide some protection against retinopathy in individuals with type 2 diabetes and warrants more research as a preventative option.
DIAGNOSTIC YIELD OF IN VITRO VITREOUS BIOPSY FOR INTRAOCULAR LYMPHOMA AT VARIABLE VITREOUS CUTTER SPEEDS USING 25-GAUGE VITRECTOMY
Authors: Tekumalla Sruti , Xu David , Awh Katherine , Philp Nancy , Milman Tatyana , Garg Sunir
Published: February 2023

Purpose:

Primary vitreoretinal lymphoma is the most common intraocular lymphoproliferative disorder. We evaluated the diagnostic yield of pars plana vitrectomy, specifically using modern high cut rate dual-cycle cutters, on in vitro cell viability and diagnostic yield.

Methods:

Human Burkitt lymphoma cell line Namalwa at 2 x 10^5 cells/mL was aspirated by 25-gauge dual-blade guillotine-type vitrectomy at five speeds (500, 1,000, 4,000, 7,500, or 15,000 cuts per minute). Cell viability and diagnostic yield in each subtype group were determined using hemocytometry, viable cell count using Cell Counting Kit-8, and pathologist-guided manual count.

Results:

No significant deviation in cell count was identified in any cut rate by ANOVA (P = 0.61), and no trends in the number of viable cells were identified across cut rates (R2 = 0.188, P = 0.47). Among histologic cell counts per cut-rate, neither linear regression (R = 0.531, P = 0.16) nor ANOVA (P = 0.096) were statistically significant.

Conclusion:

There was no significant degradation in the number of viable cells with increasing cut speed. These results suggest that in contrast to previous findings using 20g or 23g vitrectomy for diagnostic vitrectomy, modern vitrectomy systems may be used at up to 15,000 cpm without compromising the viability of lymphoma cells.
CT-quantified sarcopenic visceral obesity is associated with poor transplant waitlist mortality in patients with cirrhosis
Authors: Ha Nghiem B. , Fan Bo , Shui Amy M. , Huang Chiung-Yu , Brandman Danielle , Lai Jennifer C.
Published: February 2023

Sarcopenic obesity is associated with higher rates of morbidity and mortality than seen with either sarcopenia or obesity alone. We aimed to define sarcopenic visceral obesity (SVO) using CT-quantified skeletal muscle index and visceral-to-subcutaneous adipose tissue ratio and to examine its association with waitlist mortality in patients with cirrhosis. Included were 326 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with available abdominal CT within 6 months from enrollment between February 2015 and January 2018. SVO was defined as patients with sarcopenia (skeletal muscle index <50 cm2/m2 in men and <39 cm2/m2 in women) and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥1.21 in men and ≥0.48 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 44%, 29%, and 13%, respectively. Cumulative incidence of waitlist mortality was higher in patients with SVO compared to patients with sarcopenia without visceral obesity or visceral obesity without sarcopenia at 12 months (40% vs. 21% vs. 12%) (overall logrank p=0.003). In univariable Cox regression, SVO was associated with waitlist mortality (HR: 3.42, 95% CI: 1.58–7.39), which remained significant after adjusting for age, sex, diabetes, ascites, encephalopathy, MELDNa, liver frailty index, and different body compositions (HR: 2.64, 95% CI: 1.11–6.30). SVO was associated with increase waitlist mortality in patients with cirrhosis in the ambulatory setting awaiting liver transplantation. Concurrent loss of skeletal muscle and gain of adipose tissue seen in SVO quantified by CT may be a useful and objective measurement to identify patients at risk for suboptimal pretransplant outcomes.
Acupuncture at Hegu point (LI4) for myofascial temporomandibular disorders
Authors: Wang Fang-Li , Chu Jia-Mei , Yu Jing , Wang Qin
Published: February 2023

Rationale:

Temporomandibular disorders (TMD) are a common disease. To date, no study has reported the outcomes of acupuncture treatment of a single acupoint (LI 4) bilaterally for 1 session in patients with myofascial pain temporomandibular disorders (MTMD). This report describes the successful addition of acupuncture on pain and mandibular function in a patient with MTMD.

Patient concerns:

A 29-year-old patient reported pain on mastication, especially food of harder consistency in right preauricular area and limitation of the mouth opening for 2 years and getting worse since 1 month ago.

Diagnoses:

In this study, the diagnosis of MTMD was based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). The patient had no obvious differential diagnosis.

Interventions:

The patient received a 30-minute acupuncture treatment bilaterally at the Hegu large intestine 4 (LI 4) acupoint.

Outcomes:

All outcome measures (the visual analogueue scale, maximum mouth opening, bilateral movement) substantially improved. Moreover, during the observation period, the patient’s myofascial pain and mandibular movement did not worsen.

Lessons:

After a 30-minute acupuncture treatment, mandibular movement, function, and pain of the masticatory muscle had been improved. However, we could not rule out the possibility of an influence of the passage of time or the Hawthorne effect. The costs of the treatment of MTMD may be reduced, if this therapy was proved useful in future controlled studies.
New-onset functional dyspepsia after COVID-19
Authors: Khatri Rishabh , Patel Jay , Song Jun , Parkman Henry P.
Published: February 2023

Rationale:

Patients with severe acute respiratory syndrome coronavirus 2 may have gastrointestinal symptoms including abdominal pain and burning. However, these symptoms may be due to functional dyspepsia (FD), a heterogeneous disorder with some documented cases being due to postinfectious sequela.

Patient Concerns:

We report a case of a 57-year-old female with well-controlled celiac disease and vitamin D deficiency who developed early satiety, abdominal pain, stomach fullness, postprandial burning, and weight loss after testing positive for coronavirus disease 2019.

Diagnoses:

Her symptoms started improving with medical treatment of FD. The timeline of symptom onset, persistence, and eventual improvement suggests she had postinfectious FD as a likely sequelae of severe acute respiratory syndrome coronavirus 2 infection.

Interventions:

She failed to improve with antiemetic and anti-reflux medications, and work-up revealed no endoscopic evidence of her dyspepsia.

Outcomes:

Her symptoms started improving with medical treatment of FD.

Lessons:

This case report highlights the importance of suspecting coronavirus disease 2019 as the etiology in patients who develop dyspepsia but have no endoscopic abnormalities.
Efficacy of Infliximab Biosimilar for Maintenance Therapy in Pediatric Inflammatory Bowel Disease Following Infliximab Originator
Authors: Hinshaw Amie , Cares Kristen , Thomas Ron , El-Baba Mohammad
Published: February 2023

Objectives:

The safety, efficacy, and cost-effectiveness of Infliximab biosimilar agents in the management of inflammatory bowel disease in adults have been shown. These agents have been recommended for pediatric inflammatory bowel disease, and although institutions are initiating therapy with the biosimilar agents (IFX-B), few are switching maintenance therapy from the originator (IFX-O). The aim was to compare biochemical markers of disease activity of children with inflammatory bowel disease on maintenance therapy with IFX-B to their previous markers on IFX-O.

Methods:

Single-center, retrospective chart review of 25 children with inflammatory bowel disease who transitioned from Remicade (IFX-O) to the biosimilar agent Inflectra (IFX-B) for maintenance therapy. Analysis included demographics and various biochemical markers of disease control. The nonparametric-related samples Wilcoxon signed-rank test was used to compare mean ranks of these markers (C-reactive protein, erythrocyte sedimentation rate, hemoglobin, platelet count, albumin, body mass index z score) between the last 12 months on IFX-O and the first 12 months on IFX-B.

Results:

Between March 2018 and June 2018, the majority of patients with pediatric inflammatory bowel disease on maintenance therapy with IFX-O at our institution were transitioned to maintenance therapy with IFX-B. Of the 25 children included, 17 were diagnosed with Crohn disease and 8 with ulcerative colitis. The results of all, except albumin value, supported retention of the null hypothesis that there would not be a statistically significant difference in the biochemical markers of disease activity between the 2 medications.

Conclusions:

IFX-B is as effective as IFX-O for maintenance therapy in pediatric inflammatory bowel disease when comparing biochemical markers of disease activity.
Feeding Pathway for Children on High Flow Nasal Cannula Decreases Time to Enteral Nutrition
Authors: Soshnick Sara H. , Mark Gabriella S. , Weingarten-Arams Jacqueline , Chuu Ying , Chandhoke Swati , Medar Shivanand S. , Philips Kaitlyn , Cassel-Choudhury Gina N.
Published: February 2023

Introduction:

High Flow Nasal Cannula (HFNC) is commonly used for children with respiratory failure, yet no standardized guidelines exist on how to initiate, escalate, and maintain enteral nutrition (EN) for these patients. EN in critically ill children is associated with decreased hospital length of stay, decreased ventilator days, and fewer acquired infections. We aimed to decrease the mean time to EN initiation by 50% after the start of HFNC in 6 months.

Methods:

This quality improvement project used the Model for Improvement to inform interventions. A multidisciplinary team created an EN pathway for critically ill patients on HFNC. We conducted Plan-Do-Study-Act cycles related to implementing a standardized pathway for EN on HFNC. The primary outcome was time to EN initiation once on HFNC. Secondary outcomes were time to goal caloric EN, duration of HFNC, and adverse events. Outcomes were plotted on statistical process control charts and analyzed for special cause variation between baseline and intervention periods.

Results:

We included 112 patients in the study. Special cause variation occurred for both primary and secondary outcomes. The mean time to EN initiation decreased from 24.6 hours to 11.7 hours (47.5%). Mean time to goal feeds decreased from 25.8 hours to 15.1 hours (58.5%). Mean HFNC duration did not show any special cause variation. There were no episodes of aspiration.

Conclusion:

Implementation of a standardized pathway for EN on patients receiving HFNC resulted in decreased time to initiation of EN and time to goal caloric EN with no significant increase in adverse events.
Ade novomissense variant inEZH1associated with developmental delay exhibits functional deficits inDrosophila melanogaster
Authors: Jangam Sharayu , Briere Lauren C. , Jay Kristy , Andrews Jonathan C , Walker Melissa A. , Rodan Lance H. , High Frances A. ,   Undiagnosed Diseases Network, Yamamoto Shinya , Sweetser David A. , Wangler Michael
Published: February 2023

EZH1(Enhancer of Zeste, homolog 1), a Polycomb Repressive Complex-2 (PRC2) component, is involved in a myriad of cellular processes through modifying histone 3 lysine27 (H3K27) residues.EZH1represses transcription of downstream target genes through H3K27 trimethylation (H3K27me3). Genetic mutations in histone modifiers have been associated with developmental disorders, whileEZH1has not yet been linked to any human disease. However, the paralogEZH2is associated with Weaver syndrome. Here we report a previously undiagnosed individual with a novel neurodevelopmental phenotype identified to have ade novovariant inEZH1, p.Ala678Gly, through exome sequencing. The individual presented in infancy with neurodevelopmental delay and hypotonia and was later noted to have proximal muscle weakness. The variant, p.A678G, is in the SET domain, known for its methyltransferase activity, and was the best candidate variant found in the exome. HumanEZH1/2are homologous to flyEnhancer of zeste E(z), an essential gene in flies, and the residue (A678 in humans, A691 inDrosophila) is conserved. To further study this variant, we obtainedDrosophilanull alleles and generated transgenic flies expressing wild-type(E(z)WT)and the variant(E(z)A691G). TheE(z)A691Gvariant led to hyper H3K27me3 while theE(z)WTdid not, suggesting this is as a gain-of-function allele. When expressed under the tubulin promotorin vivothe variant rescued null-lethality similar to wild-type but theE(z)A691Gflies exhibit bang sensitivity and shortened lifespan. In conclusion, here we present a novelEZH1 de novovariant associated with a neurodevelopmental disorder. Furthermore, we found that this variant has a functional impact inDrosophila. Biochemically this allele leads to increased H3K27me3 suggesting gain-of-function, but when expressed in adult flies theE(z)A691Ghas some characteristics of partial loss-of-function which may suggest it is a more complex allelein vivo.
A Multitask Approach for Automated Detection and Segmentation of Thyroid Nodules in Ultrasound Images
Authors: Radhachandran Ashwath , Kinzel Adam , Chen Joseph , Sant Vivek , Patel Maitraya , Masamed Rinat , Arnold Corey W. , Speier William
Published: February 2023

An increase in the incidence and diagnosis of thyroid nodules and thyroid cancer underscores the need for a better approach to nodule detection and risk stratification in ultrasound (US) images that can reduce healthcare costs, patient discomfort, and unnecessary invasive procedures. However, variability in ultrasound technique and interpretation makes the diagnostic process partially subjective. Therefore, an automated approach that detects and segments nodules could improve performance on downstream tasks, such as risk stratification.Current deep learning architectures for segmentation are typically semi-automated because they are evaluated solely on images known to have nodules and do not assess ability to identify suspicious images. However, the proposed multitask approach both detects suspicious images and segments potential nodules; this allows for a clinically translatable model that aptly parallels the workflow for thyroid nodule assessment. The multitask approach is centered on an anomaly detection (AD) module that can be integrated with any U-Net architecture variant to improve image-level nodule detection. Ultrasound studies were acquired from 280 patients at UCLA Health, totaling 9,888 images, and annotated by collaborating radiologists. Of the evaluated models, a multi-scale UNet (MSUNet) with AD achieved the highest F1 score of 0.829 and image-wide Dice similarity coefficient of 0.782 on our hold-out test set. Furthermore, models were evaluated on two external validations datasets to demonstrate generalizability and robustness to data variability. Ultimately, the proposed architecture is an automated multitask method that expands on previous methods by successfully both detecting and segmenting nodules in ultrasound.
SNORD90 induces glutamatergic signaling following treatment with monoaminergic antidepressants
Authors: Lin Rixing , Kos Aron , Lopez Juan Pablo , Dine Julien , Fiori Laura M. , Yang Jennie , Ben-Efraim Yair , Aouabed Zahia , Ibrahim Pascal , Mitsuhashi Haruka , Wong Tak Pan , Ibrahim El Cherif , Belzung Catherine , Blier Pierre , Farzan Faranak , Frey Benicio N. , Lam Raymond W. , Milev Roumen , Müller Daniel J. , Parikh Sagar V. , Soares Claudio , Uher Rudolf , Nagy Corina , Mechawar Naguib , Foster Jane A. , Kennedy Sidney H. , Chen Alon , Turecki Gustavo
Published: February 2023

Most available antidepressants target the serotonergic system, selectively or non-selectively, and yield slow and inconsistent clinical responses, whereas the monoamine changes they elicit do not correlate with treatment response. Recent findings point to the glutamatergic system as a target for rapid acting antidepressants. Investigating different cohorts of depressed individuals treated with serotonergic and other monoaminergic antidepressants, we found that the expression of a small nucleolar RNA, SNORD90, was elevated following treatment response. When we increased SNORD90 levels in the mouse anterior cingulate cortex (ACC), a brain region regulating mood responses, we observed antidepressive-like behaviors. We identified neuregulin 3 (NRG3) as one of the targets of SNORD90, which we show is regulated through the accumulation of N6-methyladenosine modifications leading to YTHDF2 mediated RNA decay. We further demonstrate that a decrease in NRG3 expression resulted in increased glutamatergic release in the mouse ACC. These findings support a molecular link between monoaminergic antidepressant treatment and glutamatergic neurotransmission.
Exploring the Effectiveness of PAC Rehabilitation for the Patients with Traumatic Brain Injury : A Retrospective Study
Authors: Yang Ju-Lan , Hsu Ying-Lin , Lin Chih-Ming , Lei Ruoh-Lih
Published: February 2023

Background

According to a report from the World Health Organization, traumatic brain injury (TBI) will surpass many diseases by 2020 and become the main cause of death and disability. Therefore, post-acute care (PAC) is immediately given active integrated care during the golden period of post-acute care to restore its function, which will reduce the medical expenses of subsequent rehospitalization.

Objective

The purpose of this study was to explore the effectiveness of post-acute care for the patients with traumatic brain injury.

Methods

This is a retrospective cohort study that enrolled 168 patients over 18 years of age (inclusive) before and after PAC. The researcher collected the differences between the before and after receiving PAC collected about the Barthel Index (ADL), Lawton-Brody IADL Scale (IADL), and EuroQoL-5D(EQ-5D) by using purposive sampling. It was using machine learning and Power BI to analyze research results statistically.

Results

The results show that traumatic brain injury patients who received PAC rehabilitation had significant functional recovery effects(p-value <0.001). Additionally, the relationship between Barthel index, IADL and EQ-5D, the results show that when the Barthel index score is higher (Pearson correlation coefficient =1), the IADL score will also be higher (Pearson correlation coefficient =0.481), showing a positive correlation. When the Barthel index score is higher (Pearson correlation coefficient =1), the EQ-5D score will be lower (Pearson correlation coefficient =-0.582), showing a negative correlation. When the IADL score is higher (Pearson correlation coefficient =1), the Barthel index score will be higher (Pearson correlation coefficient =0.481), showing a positive correlation, while the EQ-5D score will be lower (Pearson correlation coefficient =-0.496), showing there is a negative correlation.

Conclusion

The results of this study confirm that PAC has essential effects. This result can be used as a reference for national planning health policies, cross-disciplinary professional design cases, and family PAC intervention plans to restore activity functions as soon as possible, improve the quality of life, and reduce the burden of family and social care.
Peripheral nerve induction of inhibitory brain circuits to treat Tourette syndrome: A randomized crossover trial
Authors: Iverson Ann M. , Arbuckle Amanda L. , Ueda Keisuke , Song David Y. , Bihun Emily C. , Koller Jonathan M. , Wallendorf Michael , Black Kevin J.
Published: February 2023

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained sensorimotor cortex EEG signal, and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested and stimulation blocks lasted only 1 minute. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity and urges without significant difference. Participant masking was effective and there was no carryover effect. Several participants described dramatic benefit. Discomfort was minimal. MNS benefit did not persist after the end of stimulation. These results replicate the tic benefit from MNS, but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain benefit; alternatively, these data do not exclude a placebo effect.

Registration

ClinicalTrials.gov,NCT04731714.
Use of focal radiotherapy boost for prostate cancer and perceived barriers toward its implementation: a survey
Authors: Zhong Allison Y. , Lui Asona J. , Katz Matthew S. , Berlin Alejandro , Kamran Sophia C. , Kishan Amar U. , Murthy Vedang , Nagar Himanshu , Seible Daniel , Stish Bradley J. , Tree Alison C. , Seibert Tyler M.
Published: February 2023

Background

In a recent phase III randomized control trial (FLAME), delivering a focal radiotherapy (RT) boost to tumors visible on MRI was shown to improve outcomes for prostate cancer patients without increasing toxicity. The aim of this study was to assess how widely this technique is being applied in current practice as well as physicians’ perceived barriers toward its implementation.

Methods

An online survey assessing the use of intraprostatic focal boost was conducted in December 2022 and February 2023. The survey link was distributed to radiation oncologists worldwide via email list, group text platform, and social media.

Results

The survey initially collected 205 responses from various countries over a two-week period in December 2022. The survey was then reopened for one week in February 2023 to allow for more participation, leading to a total of 263 responses. The highest-represented countries were the United States (42%), Mexico (13%), and the United Kingdom (8%). The majority of participants worked at an academic medical center (52%) and considered their practice to be at least partially genitourinary (GU)-subspecialized (74%).

57% of participants reportednotroutinely using intraprostatic focal boost. Even among complete subspecialists, a substantial proportion (39%) do not routinely use focal boost. Less than half of participants in both high-income and low-to-middle-income countries were shown to routinely use focal boost. The most commonly cited barriers were concerns about registration accuracy between MRI and CT (37%), concerns about risk of additional toxicity (35%), and challenges to accessing high-quality MRI (29%).

Conclusion

Despite level 1 evidence from the FLAME trial, most radiation oncologists surveyed are not routinely offering focal RT boost. Adoption of this technique might be accelerated by increased access to high-quality MRI, better registration algorithms of MRI to CT simulation images, physician education on benefit-to-harm ratio, and training on contouring prostate lesions on MRI.
Stomatal dynamics are regulated by leaf hydraulic traits and guard cell anatomy in nine true mangrove species
Authors: Qie Ya-Dong , Zhang Qi-Wei , McAdam Scott A. M. , Cao Kun-Fang
Published: February 2023

Stomatal regulation is critical for mangroves to survive water deficits and highly fluctuating ambient water availability in the hyper-saline intertidal zone. Despite the importance of stomatal regulation in mangroves very little is known about stomatal sensitivity to vapour pressure deficit (VPD), and the co-ordination of this trait with stomatal morphology and leaf hydraulic traits in these species.

We measured the stomatal response to a step increase in vapour pressure deficit (VPD)in situ, stomatal anatomy, leaf hydraulic vulnerability and pressure-volume traits in nine true mangrove species of five families. We aimed to answer two questions: (1) Does stomatal morphology determine stomatal dynamics in response to a high VPD in mangroves and (2) do leaf hydraulic traits influence stomatal sensitivity to VPD in mangroves?

We found that the stomata of mangrove plants highly sensitive to VPD, and that species with higher maximum stomatal conductance had slower stomatal responses to an increase in VPD, and that stomatal density and size were correlated with the speed of stomatal closure at high VPD across the closely-related species. We also found that a higher leaf capacitance (Cleaf) and more resistance to leaf hydraulic vulnerability were associated with slower stomatal responses to an increase in VPD.

Our results demonstrate that the dynamics of the stomatal response to an increase in VPD are regulated by leaf hydraulic traits and stomatal morphology. Our work provides a quantitative framework to better understand stomatal regulation in mangroves in an environment with highly dynamic water availability.
Calcium transients trigger switch-like discharge of prostaglandin E2in an extracellular signal-regulated kinase-dependent manner
Authors: Watabe Tetsuya , Yamahira Shinya , Takakura Kanako , Thumkeo Dean , Narumiya Shuh , Matsuda Michiyuki , Terai Kenta
Published: February 2023

Prostaglandin E2(PGE2) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE2secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin-Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors we demonstrate that calcium transients in a single cell cause PGE2-mediated radial spread of PKA activation (RSPA) in neighboring cells. Byin vivoimaging, RSPA was also observed in the basal layer of the mouse epidermis. Experiments with an optogenetic tool revealed a switch-like PGE2discharge in response to the increasing cytoplasmic Ca2+concentrations. The cell density of MDCK cells correlated with the frequencies of calcium transients and the following RSPA. The extracellular signal-regulated kinase (ERK) activation also enhanced the frequency of RSPA in MDCK andin vivo. Thus, the PGE2discharge is regulated temporally by calcium transients and ERK activity.