bluuebunny/crossref_metadata_2025 huggingface dataset:
WDR5 is required forDUX4expression and its pathological effects in FSHD muscular dystrophy
Authors: Mocciaro Emanuele , Giambruno Roberto , Micheloni Stefano , Cernilogar Filippo M , Andolfo Annapaola , Consonni Cristina , Pannese Maria , Ferri Giulia , Runfola Valeria , Schotta Gunnar , Gabellini Davide
Published: April 2023

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent neuromuscular disorders. The disease is linked to copy number reduction and/or epigenetic alterations of the D4Z4 macrosatellite on chromosome 4q35 and associated with aberrant gain of expression of the transcription factor DUX4, which triggers a pro-apoptotic transcriptional program leading to muscle wasting. As today, no cure or therapeutic option is available to FSHD patients. Given its centrality in FSHD, blocking DUX4 expression with small molecule drugs is an attractive option. We previously showed that the long non protein-coding RNA DBE-T is required for aberrant DUX4 expression in FSHD. Using affinity purification followed by proteomics, here we identified the chromatin remodeling protein WDR5 as a novel DBE-T interactor and a key player required for the biological activity of the lncRNA. We found that WDR5 is required for the expression of DUX4 and its targets in primary FSHD muscle cells. Moreover, targeting WDR5 rescues both cell viability and myogenic differentiation of FSHD patient cells. Notably, comparable results were obtained by pharmacological inhibition of WDR5. Importantly, WDR5 targeting was safe to healthy donor muscle cells. Our results support a pivotal role of WDR5 in the activation of DUX4 expression identifying a druggable target for an innovative therapeutic approach for FSHD.
Piecing together the puzzle of emotional consciousness
Authors: Engelen Tahnée , Mennella Rocco
Published: April 2023

The search for neural correlates of emotional consciousness has gained momentum in the last decades. Nonetheless, disagreements concerning the mechanisms that determine the experiential qualities of emotional consciousness—the “what is it like” to feel an emotion—as well as on their neural correlates have far-reaching consequences on how researchers study and measure emotion, sometimes leading to seemingly irresolvable impasses. The current paper lays out in a balanced way the viewpoint of both cognitive and precognitive approaches to emotional consciousness on the basis of commonalities and differences between the claims of some relevant theories of emotions. We examine the sufficiency of the existing evidence in support of the proposed theories of emotional consciousness by going through the methodological specificity of the study of emotional consciousness and its unique challenges and highlighting what can and cannot be imported by advances in research on perceptual consciousness. We propose that there are three key experimental contrasts that are each equally necessary in the search for the neural correlates of emotional consciousness and each contrast alone coming with its own limitations. We conclude by acknowledging some of the most promising avenues in the field, which may help go beyond the current limitations and collaboratively piece together the puzzle of emotional consciousness.
Ka-band cryogenic low-noise receiver of the Misasa 54 m antenna for deep-space communications and radio astronomy
Authors: Tsuboi Masato , Hasegawa Yutaka , Tabuchi Go , Murata Yasuhiro , Yuchi Koji , Toda Tomoaki , Uchimura Takashi , Kimura Kimihiro , Kasuga Takashi
Published: April 2023

We built a Ka-band dual-circular-polarization low-noise receiver for the Misasa 54 m parabola antenna in Misasa, Japan. The antenna is designed to be combined with a transmitter and receiver system at the X band (around 8 GHz) and simultaneously with a receiver system at the Ka band. The Ka band is the frequency band around 30 GHz, which is important for deep-space communications and radio astronomy. The receiver comprises some waveguide components including a feed horn, a circular polarizer, and low-noise amplifiers. The components are installed in a vacuum vessel and are cooled to 4 K with a Gifford–McMahon refrigerator, providing low-noise performance. The receiver is capable of simultaneously handling the left- and right-hand circular-polarization (LHCP and RHCP) channels. The receiver-noise temperature was measured to be TRX ≃ 14 K in both the LHCP and RHCP channels. The system-noise temperature, including the antenna loss and atmospheric attenuation at the zenith, was measured to be Tsys = 36–37 K in both the LHCP and RHCP channels on a clear day in September at Misasa. When the receiver is used with the X-band transmitter, the system-noise temperature is maintained at Tsys ≃ 42 K in the RHCP channel. The degradation in the system-noise temperature is attributed to a frequency-selective reflector, which divides the signals in the X and Ka bands. There is no contamination from the transmitter to damage the receiver. The receiver has already been in use for deep-space communications and radio-astronomy observations. Our team in the radio-astronomy laboratory of ISAS/JAXA is responsible for the development of the receiver and the measurements of its performance.
Cryoelectron microscopic structure of the nucleoprotein–RNA complex of the European filovirus, Lloviu virus
Authors: Hu Shangfan , Fujita-Fujiharu Yoko , Sugita Yukihiko , Wendt Lisa , Muramoto Yukiko , Nakano Masahiro , Hoenen Thomas , Noda Takeshi
Published: April 2023

Lloviu virus (LLOV) is a novel filovirus detected in Schreiber's bats in Europe. The isolation of the infectious LLOV from bats has raised public health concerns. However, the virological and molecular characteristics of LLOV remain largely unknown. The nucleoprotein (NP) of LLOV encapsidates the viral genomic RNA to form a helical NP-RNA complex, which acts as a scaffold for nucleocapsid formation and de novo viral RNA synthesis. In this study, using single-particle cryoelectron microscopy, we determined two structures of the LLOV NP–RNA helical complex, comprising a full-length and a C-terminally truncated NP. The two helical structures were identical, demonstrating that the N-terminal region determines the helical arrangement of the NP. The LLOV NP–RNA protomers displayed a structure similar to that in the Ebola and Marburg virus, but the spatial arrangements in the helix differed. Structure-based mutational analysis identified amino acids involved in the helical assembly and viral RNA synthesis. These structures advance our understanding of the filovirus nucleocapsid formation and provide a structural basis for the development of antifiloviral therapeutics.
Do Managers Do Good with Other People’s Money?
Authors: Cheng Ing-Haw , Hong Harrison , Shue Kelly
Published: April 2023

There is mixed evidence on whether the marginal dollar spent on corporate social responsibility is due to agency problems. We propose an approach by modeling how the 2003 dividend tax cut, which increased after-tax insider ownership and better aligned managerial and shareholder interests, affected the marginal dollar spent on firm responsibility. We confirm key predictions of our agency model: following the tax cut, moderate insider-ownership firms experience larger declines in their responsibility ratings and increases in their valuations relative to other firms. We also confirm another implication regarding managerial misalignment using a regression-discontinuity design of close votes on shareholder-governance proposals. (JEL G30, G31, G35)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Review of Major Social Determinants of Health in Schizophrenia-Spectrum Disorders: II. Assessments
Authors: Sturm Emily T , Thomas Michael L , Sares Anastasia G , Dave Subodh , Baron David , Compton Michael T , Palmer Barton W , Jester Dylan J , Jeste Dilip V
Published: April 2023

Background and Aims

Social determinants of health (SDoHs) impact the development and course of schizophrenia-spectrum psychotic disorders (SSPDs). Yet, we found no published scholarly reviews of psychometric properties and pragmatic utility of SDoH assessments among people with SSPDs. We aim to review those aspects of SDoH assessments.

Study Design

PsychInfo, PubMed, and Google Scholar databases were examined to obtain data on reliability, validity, administration process, strengths, and limitations of the measures for SDoHs identified in a paired scoping review.

Study Results

SDoHs were assessed using different approaches including self-reports, interviews, rating scales, and review of public databases. Of the major SDoHs, early-life adversities, social disconnection, racism, social fragmentation, and food insecurity had measures with satisfactory psychometric properties. Internal consistency reliabilities—evaluated in the general population for 13 measures of early-life adversities, social disconnection, racism, social fragmentation, and food insecurity—ranged from poor to excellent (0.68–0.96). The number of items varied from 1 to more than 100 and administration time ranged from less than 5 minutes to over an hour. Measures of urbanicity, low socioeconomic status, immigration status, homelessness/housing instability, and incarceration were based on public records or targeted sampling.

Conclusions

Although the reported assessments of SDoHs show promise, there is a need to develop and test brief but validated screening measures suitable for clinical application. Novel assessment tools, including objective assessments at individual and community levels utilizing new technology, and sophisticated psychometric evaluations for reliability, validity, and sensitivity to change with effective interventions are recommended, and suggestions for training curricula are offered.
Prevention of First-Episode Psychosis in People at Clinical High Risk: A Randomized Controlled, Multicentre Trial Comparing Cognitive-Behavioral Therapy and Clinical Management Plus Low-Dose Aripiprazole or Placebo (PREVENT)
Authors: Bechdolf Andreas , Müller Hendrik , Hellmich Martin , de Millas Walter , Falkai Peter , Gaebel Wolfgang , Gallinat Jürgen , Hasan Alkomiet , Heinz Andreas , Janssen Birgit , Juckel Georg , Karow Anne , Krüger-Özgürdal Seza , Lambert Martin , Maier Wolfgang , Meyer-Lindenberg Andreas , Pützfeld Verena , Rausch Franziska , Schneider Frank , Stützer Hartmut , Wobrock Thomas , Wagner Michael , Zink Mathias , Klosterkötter Joachim
Published: April 2023

Background

There is limited knowledge of whether cognitive-behavioral therapy (CBT) or second-generation antipsychotics (SGAs) should be recommended as the first-line treatment in individuals at clinical high risk for psychosis (CHRp).

Hypothesis

To examine whether individual treatment arms are superior to placebo and whether CBT is non-inferior to SGAs in preventing psychosis over 12 months of treatment.

Study Design

PREVENT was a blinded, 3-armed, randomized controlled trial comparing CBT to clinical management plus aripiprazole (CM + ARI) or plus placebo (CM + PLC) at 11 CHRp services. The primary outcome was transition to psychosis at 12 months. Analyses were by intention-to-treat.

Study Results

Two hundred eighty CHRp individuals were randomized: 129 in CBT, 96 in CM + ARI, and 55 in CM + PLC. In week 52, 21 patients in CBT, 19 in CM + ARI, and 7 in CM + PLC had transitioned to psychosis, with no significant differences between treatment arms (P = .342). Psychopathology and psychosocial functioning levels improved in all treatment arms, with no significant differences.

Conclusions

The analysis of the primary outcome transition to psychosis at 12 months and secondary outcomes symptoms and functioning did not demonstrate significant advantages of the active treatments over placebo. The conclusion is that within this trial, neither low-dose aripiprazole nor CBT offered additional benefits over clinical management and placebo.
Liver‐derived FGF21 is required for the effect of time‐restricted feeding on high‐fat diet‐induced fatty liver in mice
Authors: Hua Lun , Li Jing , Yang Yi , Jiang Dandan , Jiang Xuemei , Han Xingfa , Chao Jin , Feng Bin , Che Lianqiang , Xu Shengyu , Lin Yan , Li Jian , Fang Zhengfeng , Sun Mengmeng , Du Senyan , Luo Ting , Wu De , Zhuo Yong
Published: April 2023

Nonalcoholic fatty liver disease (NAFLD), which leads to insulin resistance, steatosis, and even hepatocellular carcinoma, is the most common chronic liver disease worldwide, however, effective treatment is still lacking. This study determined the role of liver FGF21 and the mechanisms underlying the protective effects of time‐restricted feeding (TRF) in NAFLD. FGF21 liver knockout (FGF21 LKO) mice and C57BL/6 wild‐type (WT) mice were fed either a normal or a high‐fat diet (HFD) for 16 weeks. Mice with diet‐induced obesity (DIO) were also used. The mice were fed either ad libitum or in a time‐restricted manner. Serum FGF21 levels were significantly increased after 16 weeks of TRF. TRF prevented body weight gain, improved glucose homeostasis, and protected against high‐fat diet‐induced hepatosteatosis and liver damage. The expression of genes related to liver lipogenesis and inflammation was reduced in TRF mice, but the expression of genes involved in fatty acid β‐oxidation was increased. However, those beneficial effects of TRF were blunted in the FGF21 LKO mice. Moreover, TRF promoted improvements in insulin sensitivity and liver damage in DIO mice. Our data show that liver FGF21 signaling was involved in the effect of TRF on high‐fat diet‐induced fatty liver.
Original Research: Nurses' Experiences with Racial, Ethnic, Cultural, and Religious Discrimination in the Workplace: A Qualitative Study
Authors: Saadi Altaf , Taleghani Sophia , Dillard Attallah , Ryan Gery , Heilemann MarySue , Eisenman David
Published: April 2023

Background:

As the health care workforce diversifies, understanding and addressing the lived experiences of health care professionals facing prejudice and discrimination becomes increasingly important. Previous studies have focused on physicians and medical trainees, but there remains a dearth of research exploring nurses' experiences—even though nurses make up the largest sector of the nation's health care workforce.

Objective:

This qualitative study explored nurses' experiences of personally mediated workplace discrimination based on race, ethnicity, culture, or religion.

Methods:

We conducted in-depth interviews with a convenience sample of 15 RNs at one academic medical center. Using an inductive thematic analysis approach, we identified several themes emerging from RNs' experiences and responses to a discriminatory event (“encounter”). Themes were grouped across three phases: pre-encounter, encounter, and post-encounter.

Results:

Participants reported wide-ranging experiences, from insensitive joking to overt exclusion, coming from various people including patients, patients' family members, colleagues, and physicians. For many, discrimination was cumulative: similar encounters occurred outside the workplace as well as within the clinical setting, often repeatedly, and were influenced by the sociopolitical context. Participants reported a variety of responses, including emotional reactions such as shock, fear of retaliation, and frustration at being expected to represent one's identity group. Silence or inaction predominated bystander and supervisor responses. Although the encounters themselves were fleeting, their impact was enduring. Early-career encounters were most challenging, and participants grappled internally with lasting effects for years. Long-term effects included avoidance of perpetrators, disconnection from colleagues and their own professional role, and leaving the workplace.

Conclusions:

The findings illuminate nurses' experiences with racial, ethnic, cultural, and religious discrimination in the workplace. Understanding how such discrimination affects nurses is critical to developing effective responses to encounters, creating safer workplaces, and promoting equity within the profession.
External Validation of a Prediction Model for External Cephalic Version Success
Authors: Kishkovich Thomas P. , Naert Mackenzie N. , Warsame Fowsia , Taboada Mireya P. , James Kaitlyn E. , Barth William H. , Clapp Mark A.
Published: April 2023

External cephalic version (ECV) success correlates with numerous maternal and pregnancy factors. A prior study developed an ECV success prediction model based on body mass index, parity, placental location, and fetal presentation. We performed external validation of this model using a retrospective cohort of ECV procedures from a separate institution between July 2016 and December 2021. Four hundred thirty-four ECV procedures were performed, with a 44.4% success rate (95% CI 39.8–49.2%), which was similar to the derivation cohort (40.6%, 95% CI 37.7–43.5%, P=.16). There were significant differences in patients and practices between cohorts, including the rate of neuraxial anesthesia (83.5% derivation cohort vs 10.4% our cohort, P<.001). The area under the receiver operating characteristic curve (AUROC) was 0.70 (95% CI 0.65–0.75), which was similar to that in the derivation cohort (AUROC 0.67, 95% CI 0.63–0.70). These results suggest the published ECV prediction model’s performance is generalizable outside the original study institution.
Secondary Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy for Advanced or Recurrent Mucinous Ovarian Cancer
Authors: Conley Aliyah B. , Fournier Keith F. , Sood Anil K. , Frumovitz Michael
Published: April 2023

BACKGROUND:

Advanced or recurrent primary mucinous ovarian cancer is typically incurable and associated with short progression-free and overall survival when treated with standard chemotherapy. Novel approaches are desperately needed for women with this disease.

CASES:

Two patients with advanced or recurrent primary mucinous ovarian cancer were treated with secondary cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). No additional chemotherapy was administered postoperatively. Both patients achieved a complete and durable response, with no evidence of recurrence at 21 and 27 months, respectively, after CRS with HIPEC.

CONCLUSION:

Secondary CRS with HIPEC represents a potential therapeutic option for women with recurrent primary mucinous ovarian cancer.
Associations Between Technology Use, Responsive Feeding, and Child Temperament Among Prior Prenatal Intervention Participants
Authors: Ventura Alison K. , Hart Chantelle N. , Phelan Suzanne , Jelalian Elissa , Wing Rena R.
Published: April 2023

Objectives:

The primary objective was to examine associations between mothers' television and mobile device (TV/MD) use and responsive feeding during an observed mother-toddler mealtime interaction. The secondary objective was to assess whether dimensions of child temperament were associated with mothers' TV/MD use.

Methods:

Participants from a prenatal lifestyle intervention trial to prevent excess gestational weight gain among women with overweight and obesity (N = 77) were observed during a dinner-time meal when their children were aged 19.4 ± 0.9 months. Trained video coders used the Responsiveness to Child Feeding Cues Scale to rate child strength of early/subtle, positive active, and negative active satiation cues and maternal responsiveness to these cues. Coders also recorded mothers' use of TV/MD. Child temperament was reported by mothers through the Infant Behavior Questionnaire–Revised Very Short Form.

Results:

Twelve percent (n = 9) of mothers used TV/MD during the mealtime interaction. Children whose mothers used TV/MD exhibited stronger early/subtle cues (4.1 ± 0.4) compared with children whose mothers did not use TV/MD (3.4 ± 0.2; p = 0.04). Mothers who used TV/MD exhibited significantly lower responsiveness to child satiation cues (2.0 ± 0.4) than those who did not use TV/MD (3.4 ± 0.2; p = 0.001). Greater child temperamental negative affectivity was associated with a greater likelihood of maternal TV/MD use (OR = 4.80, 95% CI = 1.21, 19.03).

Conclusion:

Mothers' TV/MD use was associated with greater child temperamental negative affectivity and lower responsiveness to child cues.
Through the Webcam: Impact of Telehealth on Developmental and Behavioral Pediatric Fellowship Training
Authors: Hung Kimberly T. , Branch Jacqueline M. , McManus Mark D. , Brown Miraides , Langkamp Diane L.
Published: April 2023

Objective:

The purpose of this study was to examine how fellowship program directors (PDs) and their fellows perceived the impact of telehealth on fellowship education in developmental behavioral pediatrics (DBP) during the COVID-19 pandemic.

Methods:

Two surveys were designed targeting DBP PDs and fellows and were distributed by e-mail from January to May 2021. Surveys consisted of closed-ended and open-ended questions about telehealth's impact on didactics, clinical teaching, and clinical experience. Analyses included descriptive statistics, Fisher's exact test, χ2 test, and qualitative classical content analysis.

Results:

A total of 31 PDs (82%) and 62 fellows (51%) responded. Before the pandemic, 0% of programs had fellows do telehealth visits at least weekly vs during the pandemic, and 85% of the programs had fellows conduct telehealth video visits at least once/week (p < 0.001). PDs and fellows agreed on many advantages of learning through telehealth particularly preceptors giving “real-time” feedback by private text messages and being able to observe fellow-run encounters unobtrusively. Ninety-four percent of fellows and 100% of fellowship directors believe that telehealth should be a formal part of DBP fellowship training even if in-clinic visits are available.

Conclusion:

Prepandemic and pandemic learning experiences differed significantly. PDs and fellows shared similar perceptions on how telehealth affected fellow education, except how telehealth affected didactics. Institutions varied in how telehealth was used to teach fellows, but many reported they found benefit in giving real-time feedback using chat functions during telehealth appointments. DBP fellowship programs should consider providing specific guidance to effectively teach telehealth to fellows.
The Increase in Hemoglobin Concentration With Altitude Differs Between World Regions and Is Less in Children Than in Adults
Authors: Mairbäurl Heimo , Kilian Samuel , Seide Svenja , Muckenthaler Martina U. , Gassmann Max , Benedict Rukundo K.
Published: April 2023

To compensate for decreased oxygen partial pressure, high-altitude residents increase hemoglobin concentrations [Hb]. The elevation varies between world regions, posing problems in defining cutoff values for anemia or polycythemia. The currently used altitude adjustments (World Health Organization [WHO]), however, do not account for regional differences. Data from The Demographic and Health Survey (DHS) Program were analyzed from 32 countries harboring >4% of residents at altitudes above 1000 m. [Hb]-increase, (ΔHb/km altitude) was calculated by linear regression analysis. Tables show 95% reference intervals (RIs) for different altitude ranges, world regions, and age groups. The prevalence of anemia and polycythemia was calculated using regressions in comparison to WHO adjustments. The most pronounced Δ[Hb]/km was found in East Africans and South Americans while [Hb] increased least in South/South-East Asia. In African regions and Middle East, [Hb] was decreased in some altitude regions showing inconsistent changes in different age groups. Of note, in all regions, the Δ[Hb]/km was lower in children than in adults, and in the Middle East, it was even negative. Overall, the Δ[Hb]/km from our analysis differed from the region-independent adjustments currently suggested by the WHO resulting in a lower anemia prevalence at very high altitudes. The distinct patterns of Δ[Hb] with altitude in residents from different world regions imply that one single, region-independent correction factor for altitude is not be applicable for diagnosing abnormal [Hb]. Therefore, we provide regression coefficients and reference-tables that are specific for world regions and altitude ranges to improve diagnosing abnormal [Hb].
Identifying Early Infections in the Setting of CRS With Routine and Exploratory Serum Proteomics and the HT10 Score Following CD19 CAR-T for Relapsed/Refractory B-NHL
Authors: Rejeski Kai , Blumenberg Viktoria , Iacoboni Gloria , Lopez-Corral Lucia , Kharboutli Soraya , Hernani Rafael , Petrera Agnese , Müller Niklas , Hildebrand Friederike , Frölich Lisa , Karschnia Philipp , Schmidt Christian , Cordas dos Santos David M. , Piñana José Luis , Müller Fabian , Martin Ana Africa , Dreyling Martin , von Bergwelt-Baildon Michael , Barba Pere , Subklewe Marion , Bücklein Veit L.
Published: April 2023

Early fever after chimeric antigen receptor T-cell (CAR-T) therapy can reflect both an infection or cytokine release syndrome (CRS). Identifying early infections in the setting of CRS and neutropenia represents an unresolved clinical challenge. In this retrospective observational analysis, early fever events (day 0–30) were characterized as infection versus CRS in 62 patients treated with standard-of-care CD19.CAR-T for relapsed/refractory B-cell non-Hodgkin lymphoma. Routine serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], procalcitonin [PCT]) were recorded daily. Exploratory plasma proteomics were performed longitudinally in 52 patients using a multiplex proximity extension assay (Olink proteomics). Compared with the CRSonly cohort, we noted increased event-day IL-6 (median 2243 versus 64 pg/mL, P = 0.03) and particularly high PCT levels (median 1.6 versus 0.3 µg/L, P < 0.0001) in the patients that developed severe infections. For PCT, an optimal discriminatory threshold of 1.5 µg/L was established (area under the receiver operating characteristic curve [AUCROC] = 0.78). Next, we incorporated day-of-fever PCT levels with the patient-individual CAR-HEMATOTOX score. In a multicenter validation cohort (n = 125), we confirmed the discriminatory capacity of this so-called HT10 score for early infections at first fever (AUCROC = 0.87, P < 0.0001, sens. 86%, spec. 86%). Additionally, Olink proteomics revealed pronounced immune dysregulation and endothelial dysfunction in patients with severe infections as evidenced by an increased ANGPT2/1 ratio and an altered CD40/CD40L-axis. In conclusion, the high discriminatory capacity of the HT10 score for infections highlights the advantage of dynamic risk assessment and supports the incorporation of PCT into routine inflammatory panels. Candidate markers from Olink proteomics may further refine risk-stratification. If validated prospectively, the score will enable risk-adapted decisions on antibiotic use.
Erythematous Papules and Nodules on the Left Arm
Authors: Berlin Brittany L. , Sarro Robert A.
Published: April 2023

An 81-year-old man was found to have pruritic papules and nodules spreading on his left arm over the past 2 weeks. Readers will be asked to identify the correct diagnosis based on history and clinical presentation. The purpose of this case is to improve diagnostic skills to properly recognize this condition and provide the appropriate treatment.
An Educational Initiative for Family Nurse Practitioners to Detect Melanoma Skin Cancer
Authors: Heathcotte Kimberly , Swenty Connie , Schaar Gina
Published: April 2023

Background

Skin cancer is the most common type of cancer in the United States. Melanoma skin cancer is the deadliest form of skin cancer. In the United States, the rates of melanoma skin cancer continue to rise more than any other type of cancer.

Local Problem

Nurse practitioners play an important role in early detection of skin cancer; however, minimal time is spent on dermatology training in current nurse practitioner programs to sufficiently prepare nurse practitioners to identify melanoma skin cancer. Early detection of melanoma skin cancer leads to decreased mortality.

Methodology

There were approximately 75 family nurse practitioners eligible to participate. The potential participants were asked to complete the online demographic survey and a pretest questionnaire. After intervention, the participants were asked to complete a posttest questionnaire.

Intervention

A web-based educational tool regarding identification of melanoma skin cancer was developed. The family nurse practitioners viewed the web-based educational module regarding melanoma skin cancer.

Results

A comparison of pretest and posttest means from the questionnaire was analyzed using a t test. Thirty-three family nurse practitioners showed statistically significant improvements in knowledge after the educational intervention. In addition, confidence increased in their ability to detect melanoma skin cancer.

Conclusions

This project has shown that a web-based educational module can improve family nurse practitioners' ability and confidence to detect melanoma skin cancer. This educational module was statistically effective and provides an educational framework that can be adopted by other healthcare organizations to improve nurse practitioner knowledge surrounding melanoma detection.
‘Man-in-the-barrel’ syndrome: a case report of bilateral arm paresis following cardiac arrest
Authors: Riyaz Romana , Usaid Syed A. , Arram Niharikha , Khatroth Sumalatha , Shah Pranita , Shrestha Abhigan B.
Published: April 2023

Background:

‘Man-in-the-barrel syndrome’ (MIBS) is a neurological phenotype with brachial diplegia, normal sensation, and preserved motor function of the lower limb. Severe hypotension leading to watershed infarctions leading to this phenotype has been reported. The pathogenesis of MIBS is believed to be cerebral hypoperfusion leading to border zone infarctions between the territories of the anterior and middle cerebral arteries.

Case Report and Discussion:

A 49-year-old chronic alcoholic hypertensive Indian male was evaluated for barrel syndrome after a cardiac arrest. MRI confirmed hyperintensities between the territories of the anterior and middle cerebral arteries bilaterally.

Conclusion:

Person in barrel syndrome is a rare neurological syndrome. MIB is common after cerebral hypoperfusion and carries a poor prognosis. Identification of the underlying cause is important because the management and prognosis vary based on the etiology.
An Indonesian female with pulmonary cystic hamartoma: a case report and literature review
Authors: Khusnurrokhman Gemilang , Febriani Anna , Wiratama Priangga A. , Widyoningroem Anita
Published: April 2023

Introduction:

Pulmonary cystic hamartoma is a rare benign cystic mass of the lung with clinical symptoms and radiological features that are not typical.

Case presentation:

A 43-year-old Indonesian female complained of chest and right shoulder pain, especially in the right clavicle. The patient underwent a chest X-ray and computed tomography scan thorax contrast, resulting in an anterior mediastinal tumor. The patient underwent wedge resection, and anatomical pathology showed pulmonary cystic hamartoma. The patient experienced postsurgery improvement.

Discussion:

Pulmonary cystic hamartoma does not have typical signs and symptoms. Pulmonary hamartoma diagnosis cannot be confirmed until a pathology anatomy examination is performed. Wedge resection is the first choice to treat pulmonary cystic hamartoma.

Conclusion:

Pulmonary cystic hamartoma is diagnosed with examination from pathology anatomy.
Retroperitoneal bronchogenic cyst resembling an adrenal tumor in adult: Three case reports and literature review
Authors: Yang Bin , Liu Lei , Tian Xiaojun , Hou Xiaofei , Lu Min , Ma Lulin
Published: April 2023

Introduction and importance:

Bronchogenic cyst is a rare congenital malformation of the tracheobronchial bud originating from the primitive foregut, especially in the retroperitoneal region. Retroperitoneal bronchogenic cysts in adults are difficult to make an accurate diagnosis preoperatively.

Case presentation:

We present three cases of retroperitoneal bronchogenic cysts resembling adrenal tumors in adults. Three cases were asymptomatic, and all were located on the left side. There was no significant enhancement of the cyst walls on contrast-enhanced computed tomography. Two cases presented with typical multilocular sacs and scattered calcification on radiology, whereas the other one showed unilocular sacs, without calcification, and elevation of serum carbohydrate antigen (CA) 19-9 and CA 24-2. Three cases underwent retroperitoneal laparoscopic surgeries. Histopathologic examination confirmed the diagnosis of retroperitoneal bronchogenic cysts. There was no recurrence of the three cases during follow-up.

Clinical Discussion:

A retroperitoneal bronchogenic cyst is mostly asymptomatic. It can be found in adults with variable findings in computed tomography. It can be likely ignored and misdiagnosed as an adrenal tumor.

Conclusion:

The tests of CA 19-9 and CA 24-2 could help diagnose retroperitoneal bronchogenic cysts. Retroperitoneal laparoscopic surgery is recommended for the treatment of retroperitoneal bronchogenic cysts with a favorable prognosis.
Successful surgical resection of a complicated left ventricular diverticulum in a neonate presented with unexplained anemia: a case report
Authors: Shrateh Oadi N. , Abusamra Muttaz M.M. , Abudaoud Majdi A. , Srour Moayad A. , Hijjeh Nizar , Haymouni Nidal , Sbeitan Iyad , Abdelraziq Samer , Abutaqa Mohammed
Published: April 2023

Introduction:

Congenital left ventricular diverticulum (LVD) is a rare congenital cardiac anomaly and may be complicated by fatal adverse events such as diverticulum rupture. Most LVD cases are asymptomatic and often discovered incidentally. Herein, we describe an unusual and peculiar clinical presentation with felicitous surgical management of ruptured LVD.

Case presentations:

A 10-day-old male infant presented with severe, intractable, and unexplained anemia associated with respiratory distress. Upon admission, the patient was clinically shocked with a hemoglobin level of 6.0 g/dl. As chest imaging showed cardiomegaly, echocardiography was performed and revealed a 9×10 mm diverticulum arising from the posterolateral wall of the left ventricle along with blood and clot collection in the pericardium. The patient underwent an urgent surgical resection of the diverticulum. He was followed up for 2 years without any readmissions or cardiac complaints.

Clinical discussion:

Systemic thromboembolism, heart failure, infarction, and tachyarrhythmias have all been reported as complications of LVD. The most serious complication is diverticulum rupture, which can result in death. As a result, this congenital defect should be discovered early to determine the potential risks and plan appropriate treatment.

Conclusion:

Congenital heart defects such as LVD should be suspected in neonates presenting with unexplained and intractable anemia. To avoid the diagnosis confusion and risk of serious complications in LVD patients, such as spontaneous rupture of the diverticulum, we advocate immediate surgical management of LVD in children.
Laparoscopic surgery for the diagnosis of abdominal effusion in the modern era of imaging – a retrospective study in a low-to-middle-income country
Authors: Quoc Ai Dang , Thi Thuy Hang Ha , Que Son Tran
Published: April 2023

Introduction:

Intraperitoneal ascites is a consequence or combination of many different underlying diseases. Laparoscopy with peritoneal biopsy is a tool for rapid and accurate diagnosis.

Methods:

We retrospectively identified patients who could not be diagnosed by clinical examination, laboratory investigations, and imaging tests.

Results:

A total of 103 (55 male and 48 female) patients were selected. The median age of the study group was 54 years (range 38–64 years). Typical clinical symptoms included fever (58.2%), abdominal pain (56.3%), and digestive disorders (62.1%). Fever and digestive disorders were higher in the peritoneal tuberculosis (TB) group than in the metastatic cancer group [(62.1% vs. 12.5%, P=0.009) and (66.3% vs. 12.5%, P=0.004)]. Abdominal pain was more common in the metastatic cancer group than in the other groups (100% vs. 55.8%, P=0.020). Patients in the TB and chronic inflammation groups had lower red blood cell counts and blood albumin (41 vs. 42, P=0.039) than those in the metastatic cancer group, respectively. The rate of intestinal wall thickening on ultrasound and peritoneal thickening on computed tomography was higher in the cancer group than in the benign group (87.5% vs. 7.4%, P=0.000) (75% vs. 23.2%, P=0.005), respectively. There was no difference in the median peritoneal fluid volume between the two groups (390 vs. 340, P=0.058). Pathological results showed 88.3%, 7.8%, and 3.9% of peritoneal TB, metastatic cancer, and chronic inflammatory lesions, respectively. The median hospital stay did not differ between the two groups (4 vs. 3 days, P=0.051). Both groups of patients had no morbidity or mortality.

Conclusion:

Unidentified ascites and peritonitis must be difficult for making diagnose by conventional methods. Laparoscopy might be supportive of making a rapid diagnosis and starting early treatment.
Novel Noninvasive Biomarkers in Liver Transplantation: A Tool on the Doorstep of Clinical Utilization
Authors: Merola Jonathan , Emond Jean C. , Levitsky Josh
Published: April 2023

Biomarkers have the potential to transform the detection, treatment, and outcomes of liver transplant complications, though their application is limited because of the lack of prospective validation. Although many genetic, proteomic, and immune markers correlating with allograft rejection and graft dysfunction have been described, evaluation of these markers in combination and validation among a broad liver transplant recipient population remain understudied. In this review, we present evidence supporting biomarker applications in 5 clinical liver transplant scenarios: (i) diagnosis of allograft rejection, (ii) prediction of allograft rejection, (iii) minimization of immunosuppression, (iv) detection of fibrosis and recurrent disease, and (v) prediction of renal recovery following liver transplantation. Current limitations for biomarker utilization and opportunities for further investigation are discussed. Accurate risk assessment, diagnosis, and evaluation of treatment responses using such noninvasive tools will pave the way for a more personalized and precise approach to management of the liver transplant patients that has profound potential to reduce morbidity and improve graft and patient longevity.
Time series prediction for the epidemic trends of monkeypox using the ARIMA, exponential smoothing, GM (1, 1) and LSTM deep learning methods
Authors: Wei Wudi , Wang Gang , Tao Xing , Luo Qiang , Chen Lixiang , Bao Xiuli , Liu Yuxuan , Jiang Junjun , Liang Hao , Ye Li
Published: April 2023

Monkeypox is a critical public health emergency with international implications. Few confirmed monkeypox cases had previously been reported outside endemic countries. However, since May 2022, the number of monkeypox infections has increased exponentially in non-endemic countries, especially in North America and Europe. The objective of this study was to develop optimal models for predicting daily cumulative confirmed monkeypox cases to help improve public health strategies. Autoregressive integrated moving average (ARIMA), exponential smoothing, long short-term memory (LSTM) and GM (1, 1) models were employed to fit the cumulative cases in the world, the USA, Spain, Germany, the UK and France. Performance was evaluated by minimum mean absolute percentage error (MAPE), among other metrics. The ARIMA (2, 2, 1) model performed best on the global monkeypox dataset, with a MAPE value of 0.040, while ARIMA (2, 2, 3) performed the best on the USA and French datasets, with MAPE values of 0.164 and 0.043, respectively. The exponential smoothing model showed superior performance on the Spanish, German and UK datasets, with MAPE values of 0.043, 0.015 and 0.021, respectively. In conclusion, an appropriate model should be selected according to the local epidemic characteristics, which is crucial for monitoring the monkeypox epidemic. Monkeypox epidemics remain severe, especially in North America and Europe, e.g. in the USA and Spain. The development of a comprehensive, evidence-based scientific programme at all levels is critical to controlling the spread of monkeypox infection.
Increased clonality among Neisseria gonorrhoeae isolates during the COVID-19 pandemic in Amsterdam, the Netherlands
Authors: Zondag H.C.A. , de Korne-Elenbaas J. , Bruisten S.M. , de Vries H.J.C. , van Dam A.P.
Published: April 2023

Distancing measures during the COVID-19 lockdown led to a temporary decrease of casual sex partners among clients of the Centre for Sexual Health (CSH) in Amsterdam, the Netherlands. We investigated the effect of this change on the genotypic and phenotypic distribution of

Neisseria gonorrhoeae

(Ng) isolates from CSH patients. From each Ng-positive patient we sequenced one isolate, resulting in 322 isolates which constituted two groups: 181 isolates cultured from 15 January to 29 February 2020 (before the first lockdown) and 141 cultured from 15 May to 30 June 2020 (during the first lockdown). Patient characteristics showed significantly more symptomatic patients and significantly fewer reported sex partners during the lockdown. Phenotypic data showed an increase in low-level azithromycin resistance and ceftriaxone susceptibility during the lockdown, and this remained after the study period. The diversity in sequence types (STs) decreased slightly during the lockdown. A shift occurred from ST 8156 being predominant before lockdown to ST 9362 during lockdown and a remarkably low median SNP distance of 17 SNPs was found between ST 9362 isolates obtained during lockdown. These findings reflect restricted travel and the change in sexual behaviour of CSH clients during the lockdown, with a potentially increased local transmission of the ST 9362 strain during this period, which led to genotypic and phenotypic changes in the Ng population. This shows that public health measures have far-reaching consequences and should be considered in the surveillance of other infectious diseases.
TGF-β induces matrisome pathological alterations and EMT in patient-derived prostate cancer tumoroids
Authors: Fernandes Soraia , La Cruz Jorge Oliver-De , Cassani Marco , Morazzo Sofia , Ďuríková Helena , Caravella Alessio , Fiore Piergiuseppe , Azzato Giulia , De Marco Giuseppe , Lauria Agostino , Izzi Valerio , Bosáková Veronika , Fric Jan , Filipensky Petr , Forte Giancarlo
Published: April 2023

Extracellular matrix (ECM) tumorigenic alterations resulting in high matrix deposition and stiffening are hallmarks of adenocarcinomas and are collectively defined asdesmoplasia. Here, we thoroughly analysed primary prostate cancer tissues obtained from numerous patients undergoing radical prostatectomy to highlight reproducible structural changes in the ECM leading to the loss of the glandular architecture. Starting from patient cells, we established prostate cancer tumoroids (PCTs) and demonstrated they require TGF-β signalling pathway activity to preserve phenotypical and structural similarities with the tissue of origin. By modulating TGF-β signalling pathway in PCTs, we unveiled its role in ECM accumulation and remodelling in prostate cancer. We also found that TGF-β-induced ECM remodelling is responsible for the initiation of prostate cell epithelial-to-mesenchymal transition (EMT) and the acquisition of a migratory, invasive phenotype. Our findings highlight the cooperative role of TGF-β signalling and ECMdesmoplasiain prompting prostate cell EMT and promoting tumour progression and dissemination
Spatio-temporal dynamics of the proton motive force on single bacterial cells
Authors: Biquet-Bisquert Anaïs , Carrio Baptiste , Meyer Nathan , Fernandes Thales F.D. , Abkarian Manouk , Seduk Farida , Magalon Axel , Nord Ashley L. , Pedaci Francesco
Published: April 2023

Electrochemical gradients established across biological membranes are fundamental in the bioenergetics of all forms of life. In bacteria, the proton motive force (PMF), the electrochemical potential associated to protons, powers an impressive array of fundamental processes, from ATP production to motility. While far from equilibrium, it has classically been considered homeostatic in time and space. Yet, recent experiments have revealed rich temporal dynamics at the single cell level and functional spatial dynamics at the scale of multicellular communities. Lateral segregation of supramolecular respiratory complexes begs the question of whether spatial heterogeneity of the PMF exists even at the single cell level. By using a light-activated proton pump as a spatially and temporally modulatable source, and the bacterial flagellar motor as a local electro-mechanical gauge, we both perturb and probe the PMF on single cells. Using global perturbations, we resolve temporal dynamics on the ms time scale and observe an asymmetrical capacitive response of the cell. Using localized perturbations, we find that the PMF is rapidly homogenized along the entire cell, faster than proton diffusion can allow. Instead, the electrical response can be explained in terms of electrotonic potential spread, as found in passive neurons and described by cable theory. This implies a global coupling between PMF sources and consumers in the bacterial membrane, excluding a sustained spatial heterogeneity while allowing for fast temporal dynamics.

Significance

Storing energy in the form of a proton gradient across a membrane is a fundamental feature of living systems. In mitochondria, spatial compartmentalization separates electrically distinct regions. In bacteria, it is unclear how this energy reservoir, the proton motive force, behaves at the single cell level: can it be heterogeneous in space as in mitochondria? How fast can it change in time? Using a light-driven proton pump and the flagellar motor as a local electro-mechanical gauge, we find that the bacterial proton motive force can change in a few tens of milliseconds, and that it is instantaneously homogenized along the membrane. This electrophysiological response is surprisingly similar to electrotonic voltage spread in passive neurons.
Reconstruction Set Test (RESET): a computationally efficient method for single sample gene set testing based on randomized reduced rank reconstruction error
Authors: Frost H. Robert
Published: April 2023

We have developed a new, and analytically novel, single sample gene set testing method called Reconstruction Set Test (RESET). RESET quantifies gene set importance at both the sample-level and for the entire dataset based on the ability of set genes to reconstruct values for all measured genes. RESET addresses four important limitations of current techniques: 1) existing single sample methods are designed to detect mean differences and struggle to identify differential correlation patterns, 2) computationally efficient techniques are self-contained methods and cannot directly detect competitive scenarios where set genes differ from non-set genes in the same sample, 3) the scores generated by current methods can only be accurately compared across samples for a single set and not between sets, and 4) the computational performance of even the fastest existing methods be significant on very large datasets. RESET is realized using a computationally efficient randomized reduced rank reconstruction algorithm (available via the RESET R package on CRAN) that can effectively detect patterns of differential abundance and differential correlation for self-contained and competitive scenarios. As demonstrated using real and simulated scRNA-seq data, RESET provides superior accuracy at a lower computational cost relative to other single sample approaches.