bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystic Features in Renal Epithelial Neoplasms and Their Increasing Clinical and Pathologic Significance
Authors: Tretiakova Maria , Kwon Jung Woo , Paner Gladell P.
Published: March 2024

Most cystic renal tumors after resection (Boniak IIF to IV cysts) have an indolent course despite the significantly higher proportion of malignant [ie, renal cell carcinoma (RCC)] diagnosis. Most cystic renal tumors have clear cell histology that include cystic clear cell RCC and multilocular cystic renal neoplasm of low malignant potential (MCNLMP). There is growing evidence to suggest that MCNLMP, cystic clear cell RCC, and noncystic clear cell RCC form a cystic-to-solid biological spectrum with MCNLMP representing the most indolent form and with cystic clear cell RCC behaving better than noncystic (solid) clear cell RCC. Extensively (>75%) cystic clear cell RCC also has an excellent outcome similar to MCNLMP stressing the need to reevaluate the histologic criteria that separate these 2 cystic clear cell tumors. Other tumors with clear cells that can be extensively cystic such as the recently reclassified noncancerous clear cell papillary renal tumor and the newly described MED15::TFE3 RCC also have indolent course and may mimic MCNLMP. Cystic features occur also in renal tumors with nonclear cell histology including tumors capable of metastasis such as acquired cystic disease-associated, tubulocystic, fumarate hydratase-deficient, and eosinophilic solid and cystic RCCs. Cystic imaging presentation of some renal tumors such as papillary RCC can be attributed in part to pseudocystic necrosis and hemorrhage. It is important to know that tubulocystic RCC may have a lower Bosniak class presentation that overlaps with benign renal cysts (Bosniak I to IIF) that are managed conservatively. This review highlights the cystic renal tumors with clear cell and nonclear cell morphologies including some novel RCC subtypes that may have cystic features. The presence of cystic features and their extent may aid in the classification and prognostication of renal neoplasms underscoring its increasing importance in the pathologic diagnosis and reporting of renal neoplasia.
NKX3.1 Expression in Non-Prostatic Tumors and Characterizing its Expression in Esophageal/Gastroesophageal Adenocarcinoma
Authors: Mehreen Ansa , Manjee Kiran G. , Paralkar Divyangi , Paner Gladell P. , Lan Thanh
Published: March 2024

The NKX3.1 immunohistochemical stain is widely recognized as a highly sensitive and specific marker for prostate adenocarcinoma. Nevertheless, its expression has been documented in various nonprostatic tissues and malignancies. This review aims to provide an overview of NKX3.1 expression in diverse tumor types, with a specific focus on its aberrant expression in esophageal/gastroesophageal adenocarcinoma (E/GE-ADC). In our investigation, we explored the expression of NKX3.1 in a series of E/GE-ADC to shed light on its prevalence in this tumor category. A total of 50 samples, comprising primary and metastatic E/GE-ADC specimens from 34 patients, were subjected to immunohistochemical analysis. Stained sections were scored based on the intensity and distribution—categorized as negative, weak, moderate, or strong in either a focal or diffuse pattern. Strong staining corresponds to the intensity observed in normal prostate controls, while focal and diffuse staining denote <50% and ≥50% of tumor nuclei staining positive, respectively. Our semiquantitative scoring revealed that 6 (12%) of the primary and metastatic E/GE-ADC specimens exhibited variable positivity for NKX3.1. This finding suggests that E/GE-ADC can sporadically stain positive for NKX3.1, introducing potential challenges in definitively determining the primary site of origin in certain clinical scenarios. Along with a literature review of NKX3.1 expression in other tumor types, our study provides additional important information about the extent to which this immunostain can be seen in E/GE-ADCs, which, to our knowledge, has not been reported.
Formulary Coverage of Esketamine and Ketamine for Depression in Ohio Health Insurance Marketplace and Medicaid Plans
Authors: Barnett Brian S.
Published: March 2024

For more than 2 decades, intravenous ketamine has been demonstrated to have rapid antidepressant effects. However, access to this generic drug is limited due to insurers claiming it is “experimental” because ketamine does not have a Food and Drug Administration indication for depression. In contrast, intranasal esketamine, an enantiomer of ketamine, is approved by the Food and Drug Administration for depression and is still under patent. The goal of this column is to provide a clearer understanding of formulary coverage of these similar medications by insurers. Formularies of all 2023 Ohio Health Insurance Marketplace and Medicaid plans were reviewed to determine the inclusion status of intravenous ketamine and intranasal esketamine for depression. This review found that intravenous ketamine was not covered by any Marketplace or Medicaid plan for depression, while intranasal esketamine was on 72.7% and 100% of formularies, respectively. Thus, members of the analyzed insurance plans can more easily access intranasal esketamine than intravenous ketamine for depression, despite the latter being more cost-effective and possibly more efficacious.
Psychotic and Somatic Symptoms Are Frequent in Refugees With Posttraumatic Stress Disorder: A Narrative Review
Authors: Gasnier Matthieu , Aouizerat Anthony , Chappell Kenneth , Baubet Thierry , Corruble Emmanuelle
Published: March 2024

Objective:

In 2021, 89.3 million refugees were vulnerable to posttraumatic stress disorder (PTSD) after exposure to multiple and repeated traumatic experiences. The recent war in Ukraine provoked 7 million refugees to flee their homes. Specific clinical presentations of PTSD in refugee populations may not be familiar to most physicians. The goal of this review is to describe the diagnosis and specific clinical features of PTSD in refugees.

Methods:

This narrative review of 263 articles explores 3 PTSD diagnoses that are frequently described in refugee populations and that have been observed in our clinical practices: complex PTSD, PTSD with psychotic symptoms, and PTSD with somatic symptoms.

Results:

While complex PTSD does not seem to be related to individuals’ culture and origin, the other 2 diagnoses have been specifically described in refugee populations. PTSD with somatic manifestations appears to be the most frequently described and commonly acknowledged form in refugee populations, whereas PTSD with psychotic symptoms remains more controversial due to its clinical variability and association with comorbid disorders.

Conclusions:

The difficulty of identifying PTSD with psychotic symptoms and PTSD with somatic symptoms in refugee populations may lead to misdiagnosis and explain the moderate effectiveness of care delivered to these populations. Appropriate diagnosis is essential to provide optimal psychiatric care to refugee populations.
Clinical Experience on the Use of a Single-day, Two-injection Start Initiation Regimen of Aripiprazole Once Monthly in Patients With Schizophrenia in Spain: SaTISfy Study
Authors: BIOQUE MIQUEL , MORENO MARÍA JOSÉ , GÓMEZ-LUS SUSANA , RAMOS MARÍA ISABEL ,   on behalf of the SaTISfy study group
Published: March 2024

Objective:

The two-injection start (TIS) initiation regimen was recently approved for aripiprazole once monthly 400 mg (AOM400), with potential benefits in adherence. The SaTISfy study described in this article analyzed Spanish psychiatrists’ perspectives on hospitalization lengths of stay, schizophrenia management, and the use of AOM400-TIS.

Methods:

The authors describe an ecological study of aggregated data collected using a 41-question survey. Fifty psychiatrists were asked to provide their perceptions of their patients with schizophrenia and treatment with AOM400.

Results:

The psychiatrists reported that lack of treatment adherence was the main reason for hospitalization for 58.3% of their patients diagnosed with schizophrenia. Aripiprazole, in any formulation, was the most commonly prescribed therapeutic option, being prescribed for a mean (SD) of 2.5 (0.9) out of 5 patients, while 98% of psychiatrists chose AOM400-TIS for patients who failed to adhere to previous treatments. Patients with schizophrenia, regardless of their treatment, were hospitalized for an average of 17.7 (3.93) days versus patients with schizophrenia treated with AOM400-TIS, who were hospitalized for an average of 14.2 (4.18) days, a reduction of 3.5 (3.86) days. Patients treated with AOM400-TIS showed a reduction of 5 (4.18) days compared with the mean national duration of hospitalization for acute patients in psychiatry units in Spain (19.18 d). The surveyed psychiatrists reported that AOM400-TIS improved safety and tolerability. Most of the psychiatrists were satisfied with the administration and results of AOM400-TIS. Most of the psychiatrists (90%) also reported that fewer health care resources were consumed with AOM400-TIS, mainly due to a reduction in hospitalization days and in the use of concomitant medications.

Conclusions:

AOM400-TIS was considered to have a positive impact on the duration of hospitalization and thus on the use of health care resources. There was a positive perception of adherence, safety, and tolerability with the use of AOM400-TIS in patients with schizophrenia.
Encephalocraniocutaneous Lipomatosis
Authors: Zaworski Emelyn , Gruber Erin , Regent-Smith Andrew , Jones Kelly L. , Chalhoub Mario Saab , Lin Kant
Published: March 2024

Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome and subclassification of oculoectodermal syndrome. Encephalocraniocutaneous lipomatosis may be associated with postzygotic mutations. However, absence of an identifiable mutation does not preclude a diagnosis of ECCL. Encephalocraniocutaneous lipomatosis commonly causes skin, eye, and central nervous system anomalies. Diagnosis can be made through genetic sequencing or standardized clinical criteria. One clinically apparent major criterion for the diagnosis of ECCL is nevus psiloliparus (NP), a fatty nevus with overlying nonscarring alopecia. In this case, a 50-day-old female infant with uncomplicated birth history presented to dermatology clinic for evaluation of 2 superficial cranial masses that had been present since birth without regression or evolution. One of the masses was located within the hairline and demonstrated overlying nonscarring alopecia, suspicious of NP. Because of concern for ECCL, brain magnetic resonance imaging was ordered and revealed 2 intracranial lipomas. Genetic testing was inconclusive. Excision of the masses was performed at the request of the parents for cosmetic purposes. Histologic evaluation of the surgical specimens confirmed the diagnosis of NP and ECCL. A suspected NP should raise concern for ECCL and prompt further evaluation for systemic involvement. In particular, patients with suspected ECCL should be screened for ocular and CNS involvement. Early identification and diagnosis are important for prognostication because patients with ECCL are at increased risk of developing neoplasms of the head and neck and may require more frequent screening examinations.
An Analysis of the Efficacy of Multilayered Repair and Reconstruction Using Combined Tissue Pedicle Flaps for Abdominal Wall Defects in Adult Bladder Exstrophy Patients
Authors: Azhati Baihetiya , Dilixiati Diliyaer , Reheman Aerziguli , Li Wentao , Yu Yang
Published: March 2024

Objective

In this study, we conducted a retrospective analysis of cases involving adult classic bladder exstrophy (CBE) accompanied by the absence of the abdominal wall. Specifically, we focused on the utilization of multilayer flaps for reconstructive purposes. In addition, we aimed to share our clinical treatment experience pertaining to similar challenges, thereby providing valuable insights to complement the surgical management of this rare disease.

Methods

We conducted a retrospective analysis of 12 adult patients diagnosed with CBE who underwent initial treatment between June 2013 and January 2020. All patients underwent multilayer reconstruction to address their abdominal wall defects. This involved utilizing shallow flaps derived from the superficial fascia of the abdomen and incorporating myofascial flaps composed of the anterior sheath of the rectus abdominis and aponeurosis of the external oblique muscle. The flap sizes ranged from 9 × 11 cm to 13 × 15 cm.

Results

Abdominal wall reconstruction in the 12 patients with CBE resulted in an absence of wound dehiscence recurrence, urinary obstruction, or urinary tract infection. All patients expressed satisfaction with the aesthetic outcome of their abdominal wall based on self-evaluation. They reported a successful resumption of normal life and work activities without experiencing any restrictions. The married patients expressed contentment with their sexual function.

Conclusion

The utilization of a multilayered reconstruction technique involving multiple flaps in adults with congenital CBE allows for successful restoration of urinary function, as well as the attainment of sufficient abdominal wall strength to support daily life and work activities, while preserving sexual function. However, it is important to approach the evaluation of surgical outcomes with caution because of the rarity of this condition and the lack of objective assessment measures.
MDIVI-1 ALLEVIATES SEPSIS-INDUCED LIVER INJURY BY INHIBITING STING SIGNALING ACTIVATION
Authors: Zhang Qin , Liu Zhuanhua , Huang Xiaoxia , Heng Xin , Wu Jie , Chen Zhenfeng , Guo Xiaohua , Fan Jun , Huang Qiaobing
Published: March 2024

Proinflammatory hyperactivation of Kupffer cells (KCs) is foremost involved in the pathogenesis of sepsis-induced liver injury. Our previous study found that stimulator of interferon genes (STING) signaling was activated in KCs in response of lipopolysaccharide (LPS) and knocking down dynamin-related protein 1 (DRP1) in KCs effectively inhibited the activation of STING signaling and the subsequent production of proinflammatory cytokines. In this study, we demonstrated that in vivo treatment with mitochondrial division inhibitor 1 (Mdivi-1), a selective inhibitor of DRP1, alleviated cecal ligation and puncture (CLP)-induced liver injury with the improvement of liver pathology and function. Moreover, we found that STING in liver was mainly concentrated in KCs and STING signaling was significantly activated in KCs after CLP. The STING deficiency effectively ameliorated liver injury and decreased the mortality of septic mice, which were reversely worsened by the enhanced activation of STING with DMXAA. The further study showed that Mdivi-1 markedly attenuated STING signaling activation in KCs and inhibited systemic inflammatory response. Importantly, DMXAA application in CLP mice blunted Mdivi-1’s liver protection effect. Taken together, our study confirmed Mdivi-1 effectively alleviated CLP-induced liver injury partially through inhibiting STING signaling activation in KCs, which provides new insights and a novel potential pharmacological therapeutic target for treating septic liver injury.
The sensitivity of limited-sequence magnetic resonance imaging in identifying pediatric cervical spine injury: A Western Pediatric Surgery Research Consortium multicenter retrospective cohort study
Authors: Melhado Caroline , Durand Rachelle , Russell Katie W. , Polukoff Natalya E. , Rampton John , Iyer Rajiv R. , Acker Shannon N. , Koehler Richele , Prendergast Connor , Stence Nicholas , O'Neill Brent , Padilla Benjamin E. , Jamshidi Ramin , Vaughn Jennifer A. , Ronecker Jennifer S. , Selesner Leigh , Lofberg Katrine , Regner Michael , Thiessen Jaclyn , Sayama Christine , Spurrier Ryan G. , Ross Erin E. , Liu Chia-Shang Jason , Chu Jason , McNevin Kathryn , Beni Catherine , Robinson Bryce R.H. , Linnau Ken , Buckley Robert T. , Chao Stephanie D. , Sabapaty Akanksha , Tong Elizabeth , Prolo Laura M. , Ignacio Romeo , Sachs Gretchen Floan , Kruk Peter , Gonda David , Ryan Mark , Pandya Samir , Koral Korgun , Braga Bruno P. , Auguste Kurtis , Jensen Aaron R. ,   on behalf of the Western Pediatric Surgery Research Consortium Cervical Spine Injury Study Group
Published: March 2024

INTRODUCTION

Clinical clearance of a child's cervical spine after trauma is often challenging because of impaired mental status or an unreliable neurologic examination. Magnetic resonance imaging (MRI) is the criterion standard for excluding ligamentous injury in children but is constrained by long image acquisition times and frequent need for anesthesia. Limited-sequence magnetic resonance imaging (LSMRI) is used in evaluating the evolution of traumatic brain injury and may also be useful for cervical spine clearance while potentially avoiding the need for anesthesia. The purpose of this study was to assess the sensitivity and negative predictive value of LSMRI as compared with criterion standard full-sequence MRI as a screening tool to rule out clinically significant ligamentous cervical spine injury.

METHODS

We conducted a 10-center, 5-year retrospective cohort study (2017–2021) of all children (0–18 years) with a cervical spine MRI after blunt trauma. Magnetic resonance imaging images were rereviewed by a study pediatric radiologist at each site to determine if the presence of an injury could be identified on limited sequences alone. Unstable cervical spine injury was determined by study neurosurgeon review at each site.

RESULTS

We identified 2,663 children younger than 18 years who underwent an MRI of the cervical spine with 1,008 injuries detected on full-sequence studies. The sensitivity and negative predictive value of LSMRI were both >99% for detecting any injury and 100% for detecting any unstable injury. Young children (younger than 5 years) were more likely to be electively intubated or sedated for cervical spine MRI.

CONCLUSION

Limited-sequence magnetic resonance imaging is reliably detects clinically significant ligamentous injury in children after blunt trauma. To decrease anesthesia use and minimize MRI time, trauma centers should develop LSMRI screening protocols for children without a reliable neurologic examination.

LEVEL OF EVIDENCE

Diagnostic Test/Criteria; Level III.
A novel preoperative score to predict severe acute cholecystitis
Authors: Kuhlenschmidt Kali , Taveras Luis R. , Schuster Kevin M , Kaafarani Haytham M. , El Hechi Majed , Puri Ruchir , Crandall Marie , Schroeppel Thomas J. , Cripps Michael W.
Published: March 2024

Background

In a large multicenter trial, The Parkland Grading Scale(PGS) for acute cholecystitis outperformed other grading scales and has a positive correlation with complications but is limited in its inability to preoperatively predict high-grade cholecystitis. We sought to identify preoperative variables predictive of high-grade cholecystitis(PGS 4 or 5).

Methods

In a six-month period, patients undergoing cholecystectomy at a single institution with prospectively graded PGS were analyzed. Stepwise logistic regression models were constructed to predict high-grade cholecystitis. The relative weight of the variables was used to derive a novel score, the Severe Acute Cholecystitis Score(SACS). This score was compared to the Emergency Surgery Acuity Score(ESS), American Association for the Surgery of Trauma(AAST) preoperative score and Tokyo Guidelines(TG) for their ability to predict high-grade cholecystitis. SACS was then validated using the database from the AAST multicenter validation of the grading scale for acute cholecystitis.

Results

Of the 575 patients that underwent cholecystectomy, 172(29.9%) were classified as high-grade. The stepwise logistic regression modeling identified 7 independent predictors of high-grade cholecystitis. From these variable the SACS was derived. Scores ranged from 0 to 9 points with a C statistic of 0.76, outperforming the ESS(C statistic of 0.60), AAST(0.53), and TG(0.70)(p-value <0.001). Using a cutoff of 4 or more on the SACS correctly identifies 76.2% of cases with a specificity of 91.3% and a sensitivity of 40.7%.

In the multicenter database, there were 464 patients with a prospectively collected PGS. The C statistic for SACS was 0.74. Using the same cutoff of 4, SACS correctly identifies 71.6% of cases with a specificity of 83.8% and a sensitivity of 52.2%.

Conclusions

The Severe Acute Cholecystitis Score can preoperatively predict high-grade cholecystitis and may be useful for counseling patients and assisting in surgical decision making.

Level of Evidence

Prognostic Level III
Impaired autophagic flux in the human brain after traumatic brain injury
Authors: Lang Jiadong , Sun Boyu , Feng Shiyao , Sun Guozhu
Published: March 2024

Emerging evidence indicates that dysfunctional autophagic flux significantly contributes to the pathology of experimental traumatic brain injury (TBI). The current study aims to clarify its role post-TBI using brain tissues from TBI patients. Histological examinations, including hematoxylin and eosin, Nissl staining, and brain water content analysis, were employed to monitor brain damage progression. Electron microscopy was used to visualize autophagic vesicles. Western blotting and immunohistochemistry were performed to analyze the levels of important autophagic flux-related proteins such as Beclin1, autophagy-related protein 5, lipidated microtubule-associated protein light-chain 3 (LC3-II), autophagic substrate sequestosome 1 (SQSTM1/p62), and cathepsin D (CTSD), a lysosomal enzyme. Immunofluorescence assays evaluated LC3 colocalization with NeuN, P62, or CTSD, and correlation analysis linked autophagy-related protein levels with brain water content and Nissl bodies. Early-stage TBI results showed increased autophagic vesicles and LC3-positive neurons, suggesting autophagosome accumulation due to enhanced initiation and reduced clearance. As TBI progressed, LC3-II and P62 levels increased, while CTSD levels decreased. This indicates autophagosome overload from impaired degradation rather than increased initiation. The study reveals a potential association between worsening brain damage and impaired autophagic flux post-TBI, positioning improved autophagic flux as a viable therapeutic target for TBI.
Neuroprotective effect of green tea extract (-)-epigallocatechin-3-gallate in a preformed fibril-induced mouse model of Parkinson’s disease
Authors: Shen Jianing , Xie Junhua , Ye Liyuan , Mao Jian , Sun Shihao , Chen Weiwei , Wei Sijia , Ruan Sisi , Wang Linhai , Hu Hangcui , Wei Jingjing , Zheng Yao , Xi Zhouyan , Wang Ke , Xu Yan
Published: March 2024

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). The main bioactive component of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) exerts protective effects against diseases such as neurodegenerative diseases and cancer. Therefore, this study investigated the effect of EGCG on the amelioration of neural damage in a chronic PD mouse model induced by α-synuclein preformed fibrils (α-syn-PFFs). A total of 20 C57BL/6J female mice were randomly divided into 3 groups: control group (saline, n = 6), model group (PFFs, n = 7), and prevention group (EGCG+PFFs, n = 7). A chronic PD mouse model was obtained by the administration of α-syn-PFFs by stereotaxic localization in the striatum. Behavioral tests were performed to evaluate PD-related anxiety-like behavior and motor impairments in the long-term PD progression. Tyrosine hydroxylase (TH) immuno-positive neurons and Ser129-phosphorylated α-syn (p-α-syn) were identified by immunohistochemistry. Pro-inflammatory and anti-inflammatory cytokines were measured by real-time quantitative PCR. EGCG pretreatment reduced anxiety-like behavior and motor impairments as revealed by the long-term behavioral test (2 weeks, 1 month, 3 months, and 6 months) on PD mice. EGCG also ameliorated PFF-induced degeneration of TH immuno-positive neurons and accumulation of p-α-syn in the SN and striatum at 6 months. Additionally, EGCG reduced the expression of pro-inflammatory cytokines while promoting the release of anti-inflammatory cytokines. EGCG exerts a neuroprotective effect on long-term progression of the PD model.
Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients
Authors: Li Peifang , Lu Honglin , Shi Xiaoman , Yan Jiajia , Zhou Lixia , Yang Jipeng , Wang Binbin , Zhao Yanying , Liu Luji , Zhu Yipu , Xu Lei , Yang Xiaoli , Su Xudong , Yang Yi , Zhang Tong , Guo Li , Liu Xiaoyun
Published: March 2024

This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann–Whitney U test; P < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group (P < 0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment (P < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).
The Prevalence of Incontinence and Its Association With Urinary Tract Infections, Dermatitis, Slips and Falls, and Behavioral Disturbances Among Older Adults in Medicare Fee-for-Service
Authors: Duncan Ian , Stocking Andrew , Fitzner Karen , Ahmed Tamim , Huynh Nhan
Published: March 2024

PURPOSE:

The purpose of this study was to examine the prevalence of urinary (UI), fecal (FI), and dual incontinence (DI) in older adults and their association with urinary tract infections, dermatitis, slips and falls, and behavioral disturbances based on Medicare fee-for-service (FFS) claims data.

DESIGN:

Retrospective analysis.

SUBJECTS AND SETTINGS:

Data from administrative claims from the CMS Medicare Limited Data Set (5% sample) for all months in 2018 were reviewed. The analysis was limited to FFS Medicare beneficiaries, with minimum of 3-month enrollment in Parts A and B who were at least 65 years old. This cohort included 1.2 million beneficiaries in the United States.

METHODS:

We used diagnosis codes to identify members with incontinence and grouped these members into 3 categories (UI only, FI only, and DI). We also divided claims based on 4 sites of care (nursing home, skilled nursing facility, home health, and self- or family care). We then determined the prevalence of (1) urinary tract infections (UTIs), (2) dermatitis, (3) slips and falls, and (4) behavioral disturbances for each type of incontinence.

RESULTS:

We found that 11.2% of Medicare members had a claims-based diagnosis of incontinence in 2018. On average, those diagnosed with incontinence experienced 5 times more UTIs, 2 times as many dermatitis events, more than twice as many slips and falls, and 2.8 times more behavior disturbances compared to those without an incontinence diagnosis. For those with DI, the prevalence of the 4 outcomes was significantly higher (between 22% and 185%) compared to those with UI only.

CONCLUSIONS:

Findings show that Medicare beneficiaries diagnosed as incontinent experience a much higher prevalence of UTIs, dermatitis, slips and falls, and behavioral disturbances compared to those without a diagnosis of incontinence. Our results suggest that incontinence may be an important indicator diagnosis for multiple other conditions and, if not well-managed, may challenge the desire for those who are incontinent to age at home.
Implementation of an Evidence-Based, Content-Validated, Standardized Support Surface Algorithm Tool in Home Health Care
Authors: Timko-Progar Monica , Drain Jerri , Stovall-Patton Kimberly
Published: March 2024

PURPOSE:

The purpose of this quality improvement project was to provide a standardized, repeatable, and easy-to-use process for selecting a support surface for prevention or treatment of pressure injuries (PIs).

PARTICIPANTS AND SETTING:

The Wound, Ostomy, and Continence Nurses Society Support Surface Algorithm was chosen to guide clinicians in selection of an appropriate support surface. These clinicians provide services to approximately 465,000 patients across the nation annually.

APPROACH:

This quality improvement project aimed to establish clinician knowledge and comfort levels when recommending a support surface and providing a standardized way to identify the appropriate support surface once a patient had been identified as at risk. The support surface algorithm was incorporated into our agency's electronic medical record (EMR); we chose this interactive algorithm to facilitate support surface selection among clinicians with no specialized expertise in PI treatment or prevention.

OUTCOMES:

Clinicians reported an increase in knowledge and comfort levels in the ability to select an appropriate support surface following implementation of the clinical decision support tool. Benchmarking data illustrated a decrease in the year over year aggregate (September 2018 to September 2021) trending for the Centers for Medicare & Medicaid Services quality outcome measures surrounding potentially avoidable events related to PIs.

IMPLICATIONS FOR PRACTICE:

Implementing the support surface algorithm assisted clinicians with support surface selection, elevated and standardized clinician practice, and reduced potentially avoidable events. As a result of this project, the Wound, Ostomy, and Continence Nurses Society Support Surface Algorithm Tool has been fully integrated into our EMR and is a standardized part of our clinical assessment.
Patient With Sitosterolemia With Slow Healing Sternal Wound From Coronary Artery Bypass Surgery
Authors: Ratliff Catherine R.
Published: March 2024

BACKGROUND:

Sitosterolemia, also known as phytosterolemia, is a rare recessive genetic disorder characterized by accumulation of sitosterol from vegetable oils, nuts, and other plant-based foods in the body. In those with sitosterolemia, there is an increase of fatty deposits in the arteries (atherosclerosis), which may occur in early childhood, impeding blood flow and increasing the risk of a heart attack, stroke, or sudden death at a very early age. Visual signs of sitosterolemia may include small yellowish xanthomas beginning in early childhood. Xanthomas are accumulated lipids that develop in the heels, elbows, and buttocks.

CASE:

A clinical case study of a patient with sitosterolemia with slow healing surgical wound from coronary artery bypass surgery is described. Treatment of sitosterolemia is aimed at lowering plasma plant sterol levels with dietary restriction intake of both animal- and plant-based sterols. However, plant-based products (collagen, chitosan, etc) are also used for wound dressings, so alternative wound dressings were selected to decrease the possibility of systemic absorption.

CONCLUSION:

This case study describes a young adult male with sitosterolemia who presented with a slow healing surgical incision following coronary artery bypass surgery. Sitosterolemia is often characterized by atherosclerosis of the coronary arteries that occurs in children and early adulthood, especially affecting men. Treatment is aimed at lowering plasma sterol levels with the restriction of animal and plant sterols. There is considerable interest today in natural versus synthetic wound care products. Dressings containing chitosan, cellulose, collagen, etc, to be avoided to decrease the chance of systemic absorption.
A 600 m
2
array of 6.5 m telescopes at the lunar pole
Authors: Angel Roger
Published: March 2024

The proposed lunar telescope for optical and infrared astronomy aims at very large aperture, 600 m
2
, at a fundable cost. It comprises an array of 18 separate telescopes, each of 6.5 m aperture. The 200 m diameter array will be located within 1/2° (15 km) of a lunar pole on approximately level ground, with a perimeter screen deployed to provide shade and cooling to cryogenic temperature. The 500 m diameter screen will allow unobscured access down to 8° elevation. All 18 telescopes will reflect light into a central beam combiner to form a single image covering wavelengths from 0.4 µm to 10 µm. The initial instrument complement will include high-resolution and multi-object spectrographs to exploit the single combined field of view of two arcminute diameter, with the diffraction limited resolution of 6.5 m aperture. Scientific applications include the search for molecular biosignatures in transiting exoplanets, and the study of galaxy evolution using red-shifted spectra to beyond
z
 = 10. The array cost, including delivery to the Moon by SpaceX Starship for installation using lunar base infrastructure, is around $10 billion, similar to that of the 25 m
2
JWST. To test the concept, first a single prototype 6.5 m unit would be operated at the lunar south pole.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 2)’.
Large-scale array for radio astronomy on the farside (LARAF)
Authors: Chen Xuelei , Gao Feng , Wu Fengquan , Zhang Yechi , Wang Tong , Liu Weilin , Zou Dali , Deng Furen , Gong Yan , He Kai , Li Jixia , Sun Shijie , Suo Nanben , Wang Yougang , Wu Pengju , Xu Jiaqin , Xu Yidong , Yue Bin , Zhang Cong , Zhou Jia , Zhou Minquan , Zhu Chenguang , Zhu Jiacong
Published: March 2024

At the Royal Society meeting in 2023, we have mainly presented our lunar orbit array concept called DSL, and also briefly introduced a concept of a lunar surface array, LARAF. As the DSL concept had been presented before, in this article, we introduce the LARAF. We propose to build an array in the far side of the Moon, with a master station which handles the data collection and processing, and 20 stations with maximum baseline of 10 km. Each station consists of 12 membrane antenna units, and the stations are connected to the master station by power line and optical fibre. The array will make interferometric observation in the 0.1–50 MHz band during the lunar night, powered by regenerated fuel cells. The whole array can be carried to the lunar surface with a heavy rocket mission, and deployed with a rover in eight months. Such an array would be an important step in the long-term development of lunar-based ultralong wavelength radio astronomy. It has a sufficiently high sensitivity to observe many radio sources in the sky, though still short of the dark age fluctuations. We discuss the possible options in the power supply, data communication, deployment etc.

This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.
Effect of CHIKV capsid protein nucleolar localisation on host gene modulation
Authors: Rao Shambhavi , West Nicholas P. , Zaid Ali , Mahalingam Suresh , Taylor Adam
Published: March 2024

Host cell nuclear localisation of alphaviral proteins has been shown to be important for host transcriptional shut off, antagonising type I interferon induction and inhibiting the antiviral response. Our previous studies demonstrate that mutation of the nucleolar localisation sequence (NoLS) of chikungunya virus (CHIKV) capsid protein significantly attenuates CHIKV replication. However, the reason for this attenuation remains unclear. In this study we investigated the impact of CHIKV capsid protein on host gene expression using Nanostring analysis and determined whether nucleolar localisation of capsid protein is required for host gene modulation. Little significant change in differential gene expression (adjusted p value <0.05) was observed in Capsid-WT-EGFP and mutant Capsid-NoLS-EGFP transfected HEK293T cells compared to mock EGFP transfected cells. To explore minor changes to host gene modulation in response to capsid protein, differential gene expression analysis was performed under a reduced arbitrary threshold (unadjusted P value < 0.01). Results suggest that, expressed as a recombinant protein, CHIKV capsid has limited impact on host gene expression, regardless of its ability to localise to the nucleolus. Results further suggest that attenuation of CHIKV resulting from mutation of the capsid protein NoLS is largely dependent on viral rather than host factors.
Enhancing COVID-19 Forecasting Precision through the Integration of Compartmental Models, Machine Learning and Variants
Authors: Baccega Daniele , Castagno Paolo , Anta Antonio Fernández , Sereno Matteo
Published: March 2024

Predicting epidemic evolution is essential for informed decision-making and guiding the implementation of necessary countermeasures. Computational models are vital tools that provide insights into illness progression and enable early detection, proactive intervention, and targeted preventive measures.

This paper introduces Sybil, a framework that integrates machine learning and variant-aware compartmental models, leveraging a fusion of data-centric and analytic methodologies. To validate and evaluate Sybil’s forecasts, we employed COVID-19 data from two European countries. The dataset included the number of new and recovered cases, fatalities, and variant presence over time. We evaluate the forecasting precision of Sybil in periods in which there is a change in the trend of the pandemic evolution or a new variant appears. Results demonstrate that Sybil outperforms a conventional data-centric approach, being able to forecast accurately the changes in the trend, the magnitude of these changes, and the future prevalence of new variants.
Analyses of academician cohorts generate biased pandemic excess death estimates
Authors: Ioannidis John P.A.
Published: March 2024

Objective

Death data from cohorts of academicians have been used to estimate pandemic excess deaths. We aimed to evaluate the validity of this approach.

Study design and setting

Data were analyzed from living and deceased member lists from Mainland China, UK and Greece academies; and Nobel laureates (and US subset thereof). Samples of early elected academicians were probed for unrecorded deaths; datasets overtly missing deaths were excluded from further analyses. Actuarial risks were compared against the general population in the same country in respective age strata. Relative incidence risk increases in death in active pandemic periods were compared to population-wide pandemic excess death estimates for the same country.

Results

Royal Society and Academy of Athens datasets overtly missed deaths. Pre-pandemic death rates were 4-12-fold lower in the Chinese Academy of Engineering (CAE) versus respective age strata of the Mainland China population. A +158% relative increase in death risk was seen in CAE data during the first 12-months of wide viral spread. Both increases (+34% in British Academy) and decreases (-27% in US Nobel laureates) in death rates occurred in pandemic (2020-22) versus pre-pandemic (2017-2019) years; point estimates were far from known excess deaths in the respective countries (+6% and +14%, respectively). Published excess death estimates for urban-dwelling Mainland China selectively analyzed CAE, but not another Chinese academy (Chinese Academy of Sciences) with half the pandemic death rates.

Conclusion

Missingness, lack of representativeness, large uncertainty, and selective analysis reporting make data from academy rosters unreliable for estimating general population excess deaths.
let-7i-5p regulates osteogenic differentiation of bone marrow mesenchymal stem cells induced by psoralen by targeting CKIP-1
Authors: Chen Ming , Zhou Song , Huang Sheng , Luo Hao , Zhang Xuelong , Liu Gangan , Li Huanan , Liu Bo , Yan Dongmei
Published: March 2024

Abstract

Previous studies have shown that psoralen can treat osteoporosis by inducing osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). CKIP-1 is an inhibitor of bone formation and plays a negative regulatory role in the osteogenic differentiation of BMSCs. MicroRNA (miRNA) is a kind of small single-stranded non-coding RNA, which regulates the occurrence and development process of cell proliferation, apoptosis, differentiation and metabolism. Studies have shown that miRNA can affect the proliferation and differentiation of BMSCs by targeting and regulating the expression of related genes. However, whether microRNA can regulate psoralen-induced osteogenic differentiation and its specific mechanisms remain unclear. The aim of this study was to identify miRNA target genes regulating the osteogenic differentiation of BMSCs induced by psoralen and further analyze the mechanism.miRNA microarray was performed to screen the differentially expressed mirnas induced by psoralen, and bioinformatics analysis and luciferase reporter gene assay were used to determine the target sites of let-7i-5p. The mechanism of let-7i-5p in psoralen induced osteogenic differentiation of BMSCs was investigated using in vitro overexpression or inhibition approaches.The results showed that miRNA microarray analysis and reverse transcription quantitative PCR further confirmed that let-7i-5p was up-regulated during the process of psoralin-induced osteogenic differentiation of BMSCs.Bioinformatics analysis and luciferase reporter gene assay confirmed CKIP-1 as a potential target of let-7i-5p.Overexpression of CKIP-1 by transfection with CKIP-1 mimetic significantly inhibited the expression of BMP, Runx2, and Smad1, while CKIP-1 inhibitor promoted their expression.Overexpression of let-7i-5p partially relieved the inhibitory effect of CKIP-1 on osteogenic differentiation of BMSCs.Our results suggest that let-7i-5p regulates psoralen-induced osteogenic differentiation of BMSCs by targeting CKIP-1, which provides a new therapeutic target for osteoporosis.
A human-aware control paradigm for human-robot interactions, a simulation study
Authors: Razavian Reza Sharif
Published: March 2024

This paper presents a novel model for predicting human movements and introduces a new control method for human-robot interaction based on this model. The developed predictive model of human movement is aholisticmodel that is based on well-supported neuroscientific and biomechanical theories of human motor control; it includes multiple levels of the human senso-rimotor system hierarchy, including high-level decision-making based on internal models, muscle synergies, and physiological muscle mechanics. Therefore, this holistic model can predict arm kinematics and neuromuscular activities in a computationally efficient way. The computational efficiency of the model also makes it suitable for repetitive predictive simulations within a robot’s control algorithm to predict the user’s behavior in human-robot interactions. Therefore, based on this model and the nonlinear model predictive control framework, ahuman-aware controlalgorithm is implemented, which internally runs simu-lations to predict the user’s interactive movement patterns in the future. Consequently, it can optimize the robot’s motor torques to minimize an index, such as the user’s neuromuscular effort. Simulation results of the holistic model and its utilization in the human-aware control of a two-link robot arm are presented. The holistic model is shown to replicate salient features of human movements. The human-aware controller’s ability to predict and minimize the user’s neuromuscular effort in a collaborative task is also demonstrated in simulation.
Effects of Age and Noise Exposure History on Auditory Nerve Response Amplitudes: A Systematic Review, Study, and Meta-Analysis
Authors: Dias James W. , McClaskey Carolyn M. , Alvey April P. , Lawson Abigail , Matthews Lois J. , Dubno Judy R. , Harris Kelly C.
Published: March 2024

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r=-0.407), but noise-exposure effects are weak (r=-0.152). We conclude that noise-exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.
Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging
Authors: Rathor Laxmi , Curry Shayla , Park Youngyong , McElroy Taylor , Robles Briana , Sheng Yi , Chen Wei-Wen , Min Kisuk , Xiao Rui , Lee Myon Hee , Han Sung Min
Published: March 2024

Mitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons inCaenorhabditis elegans(C. elegans) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism.