bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes and the risk of cirrhosis and HCC: An analysis of the UK Biobank
Authors: Ye Fangzhou , Chen Liangkai , Zheng Xin
Published: October 2023

Background:

Diabetes increases the risk of cirrhosis and HCC. We aimed to assess such associations given different diabetes statuses.

Methods:

We included 449,497 participants in the UK Biobank cohort (mean age 56.7±8.0 y; 45.5% male) and assessed the association between preclinical diabetes (prediabetes, having a high risk of diabetes), clinical diabetes (presence, duration, or glycemic control of type 2 diabetes), and incident liver cirrhosis and HCC by the Cox regression. Liver diseases were ascertained through inpatient records and national death registration. Gene-environment interaction was examined using the polygenic risk scores of cirrhosis and HCC.

Results:

Compared with normoglycemia, having <5 years,≥5 years of diabetes showed adjusted HRs (aHRs) of cirrhosis as 2.85 (2.45–3.32) and 3.43 (2.92–4.02), respectively, which was similarly observed in HCC. In diabetes, a level of hemoglobin A1c ≥ 7.5% showed aHRs of 1.37 (1.07–1.76) and 1.89 (1.10–3.25) for cirrhosis and HCC, respectively, compared with hemoglobin A1c < 6.5%. In non-diabetes, prediabetes presented aHRs of 1.41 (1.14–1.73) and 1.80 (1.06–3.04) of cirrhosis and HCC, respectively. Participants with a high risk of diabetes at baseline showed an aHR of 3.31 (2.65–4.13) for cirrhosis and 2.09 (1.15–3.80) for HCC. In those with a high genetic risk of HCC, having an increased risk of diabetes posed a significantly higher risk of HCC (aHR: 1.93, 1.45–2.58, P
interaction=0.005), compared with those without a high genetic risk of HCC.

Conclusions:

Not only diabetes but preclinical diabetes, longer diabetes duration, and higher baseline hemoglobin A1c were associated with an increased risk of incident cirrhosis and HCC in the general population.
Risk factors for intraoperative hypertensive crisis in patients with pheochromocytomas and sympathetic paragangliomas
Authors: Araujo-Castro Marta , García Sanz Iñigo , Mínguez Ojeda César , Hanzu Felicia , Mora Mireia , Vicente Almudena , Blanco Carrera Concepción , Miguel Novoa Paz de , López García María del Carmen , Lamas Cristina , Manjón-Miguélez Laura , del Castillo Tous María , Rodríguez de Vera Pablo , Barahona San Millán Rebeca , Recasens Mónica , Fernández-Ladreda Mariana Tomé , Valdés Nuria , Gracia Gimeno Paola , Robles Lazaro Cristina , Michalopoulou Theodora , Álvarez Escolá Cristina , García Centeno Rogelio , Calatayud María
Published: October 2023

Purpose:

To identify presurgical and surgical risk factors for intraoperative hypertensive crisis in patients with pheochromocytomas and sympathetic paragangliomas (PGLs) (PPGLs).

Methods:

Retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. Intraoperative hypertensive crisis was defined as systolic blood pressure (SBP) greater than 200 mmHg lasting more than 1 min and postoperative hypertensive crisis as SBP greater than 180 mmHg or diastolic blood pressure (DBP) greater than 110 mmHg.

Results:

A total of 296 surgeries were included. Alpha presurgical blockade was employed in 93.2% of the cases and beta-adrenergic in 53.4%. Hypertensive crisis occurred in 20.3% (n = 60) of the surgeries: intraoperative crisis in 56 and postoperative crisis in 6 cases (2 cases had both types of crises). We identified as risk factors of intraoperative hypertensive crisis, absence of presurgical glucocorticoid therapy (odds ratio [OR] 3.48; 95% confidence interval [CI] 1.19–10.12) higher presurgical SBP (OR 1.22 per each 10 mmHg, 95% CI 1.03–1.45), a larger tumor size (OR 1.09 per each 10 mm, 95% CI 1.00–1.19) and absence of oral sodium repletion (OR 2.59, 95% CI 1.25–5.35). Patients with hypertensive crisis had a higher rate of intraoperative bleeding (P < 0.001), of intraoperative hemodynamic instability (P < 0.001) and of intraoperative hypotensive episodes (P < 0.001) than those without hypertensive crisis.

Conclusion:

Intraoperative hypertensive crisis occurs in up to 20% of the PPGL resections. Patients not pretreated with glucocorticoid therapy before surgery, with larger tumors and higher presurgical SBP and who do not receive oral sodium repletion have a higher risk for developing hypertensive crisis during and after PPGL surgery.
NOVEL OUTER RETINAL COLUMNAR ABNORMALITIES AND NONVASOGENIC CYSTOID MACULAR EDEMA IN DENSE DEPOSIT DISEASE
Authors: Liang-Peng Claudia , Olvera-Barrios Abraham , Schwartz Roy , Grimaldi Gabriela , Egan Catherine , Tufail Adnan
Published: October 2023

Purpose:

To describe the occurrence of bilateral outer retinal columnar abnormalities, nonvasogenic cystoid macular edema, and drusen in the context of dense deposit disease.

Methods:

Case report.

Patient:

An 18-year-old girl with dense deposit disease was referred to our specialist center for diagnosis and management with findings consistent with bilateral nonvasogenic cystoid macular edema and drusen. She was followed-up in our clinic for 40 months and treated with acetazolamide and ketorolac drops.

Results:

Baseline examination revealed bilateral visual acuity reduction and macular elevation with peripapillary drusen on fundus biomicroscopy. Optical coherence tomography revealed bilateral hyporeflective cystoid central macula changes, microcystoid changes with increased central subfield thickness (>450 μm), and outer retinal columnar abnormalities. Fluorescein angiography showed no evidence of macular leakage. Electrodiagnostic testing was within normal limits. Over the course of follow-up, she received treatment with acetazolamide 250 mg twice a day by mouth and ketorolac 0.5% eye drops, with a partial reduction in her edema and improvement in visual acuity.

Conclusion:

Dense deposit disease is a rare disease secondary to complement cascade dysregulation, associated with drusen. To the best of our knowledge, this is the first report of bilateral nonvasogenic cystoid macular edema and outer retinal columnar abnormalities in a young female patient with dense deposit disease, confirmed with multimodal imaging.
A Proposal for the Use of a Fixed Low-Energy Selective Laser Trabeculoplasty for Open Angle Glaucoma
Authors: Sacks Zachary , Katz L. Jay , Gazzard Gus , Van Tassel Sarah H. , Blumenthal Eytan Z. , Lerner Fabian S. , Azuara-Blanco Augusto , Spooner Gregory John Roy , Solberg Yoram , Samuelson Thomas , Belkin Michael
Published: October 2023

Selective laser trabeculoplasty (SLT) has been in routine clinical use for over 20 years with millions of patients successfully treated and a low rate of clinically significant complications. The procedure requires the clinician to manually position the laser beam on the trabecular meshwork using a gonioscopy lens and to titrate the SLT laser energy based on the amount of pigmentation in the angle, as well as the observation of small bubbles produced by the laser effect. We propose that SLT energy titration is unnecessary either to achieve intraocular pressure (IOP) reduction or to minimize potential side effects. Ample evidence to support our proposal includes multiple clinical reports demonstrating comparable levels of IOP reduction resulting from different laser energies, a large variety of energy and other laser parameters used in commercially available SLT lasers, and the nature of the laser-induced changes in the trabecular meshwork tissue with respect to energy. Despite these variations in laser parameters, SLT consistently reduces IOP with a low complication rate. We propose that using low fixed energy for all patients will effectively and safely lower patients’ IOP while reducing the complexity of the SLT procedure, potentially making SLT accessible to more patients.
Antibody Persistence Following Administration of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T and IPV Vaccines and Safety and Immunogenicity of a Booster Dose of DTwP-IPV-HB-PRP~T Administered With an MMR Vaccine in Healthy Infants in India
Authors: Mangarule Somnath , Siddaiah Prashanth , Kawade Anand , Dhati Ravi Mandyam , Padmavathi Inumarthi Vara , Palkar Sonali , Tripathi Virendranath , Singh Raghvendra , Palvi Kudyar , Mitra Monjori , Shetty Ranjitha , Leclercq Julie , Midde Venkata Jayanth , Varghese Kucku , Kandukuri Sreeramulu Reddy , Kukian Darshna , Noriega Fernando
Published: October 2023

Background:

Antibody persistence of a whole-cell pertussis-containing hexavalent vaccine (DTwP-IPV-HB-PRP~T) and its co- or sequential administration with measles, mumps, rubella (MMR) vaccine were evaluated.

Methods:

Phase III, open-label, randomized, multicenter study in India. Healthy toddlers 12–24 months of age who had received DTwP-IPV-HB-PRP~T or separate DTwP-HB-PRP~T+IPV primary vaccination at 6–8, 10–12 and 14–16 weeks of age received a DTwP-IPV-HB-PRP~T booster concomitantly with MMR (N = 336) or 28 days before MMR (N = 340). Participants had received a first dose of measles vaccine. Immunogenicity assessment used validated assays and safety was by parental reports. All analyses were descriptive.

Results:

All participants had prebooster anti-T ≥0.01 IU/mL and anti-polio 1 and 3 ≥8 1/dil, and ≥96.5% had anti-D ≥0.01 IU/mL, anti-HBs ≥10 mIU/mL, anti-polio 2 ≥8 1/dil and anti-PRP ≥0.15 µg/mL; for pertussis, antibody persistence was similar in each group. Postbooster immunogenicity for DTwP-IPV-HB-PRP~T was similar for each antigen in each group: ≥99.5% of participants had anti-D ≥0.01 IU/mL, anti-T ≥0.01 IU/mL, anti-polio 1, 2 and 3 >8 1/dil, anti-HBs ≥10 mIU/mL and anti-PRP ≥1 µg/mL; for pertussis, vaccine response was similar in each group [72.0%–75.9% (anti-PT), 80.8%–81.4% (anti-FIM), 77.6%–79.5% (anti-PRN), 78.2%–80.8% (anti-FHA)]. There was no difference in MMR immunogenicity between groups, and no difference in DTwP-IPV-HB-PRP~T booster immunogenicity based on the primary series. There were no safety concerns.

Conclusions:

DTwP-IPV-HB-PRP~T antibody persistence was similar to licensed comparators. Booster immunogenicity was robust after DTwP-IPV-HB-PRP~T with or without MMR, and MMR immunogenicity was not affected by coadministration with DTwP-IPV-HB-PRP~T.

Clinical Trials Registry India Number:

CTRI/2020/04/024843.
Human Parechovirus Central Nervous System Infection in a Young Infant Cohort
Authors: Katragkou Aspasia , Sheth Avni , Gagliardo Christina , Aquino Jessica , Shah Niva , Nwaobasi-Iwuh Eberechi , Melchionne Christina , Black Paige , Chiu Stephanie , Di Pentima Cecilia
Published: October 2023

In 2022, a surge in cases of pediatric human parechovirus (HPeV) central nervous system infections in young infants was seen at our institution. Despite the dramatic increase in the number of cases seen that year, the clinical features of the illness were similar to prior years. The recent pediatric HPeV surge highlights the need to evaluate treatment options and standardize follow-up to better understand the long-term prognosis of infants with HPeV infection.
Biology and pathophysiology of symptomatic neuromas
Authors: Hwang Charles D. , Hoftiezer Yannick Albert J. , Raasveld Floris V. , Gomez-Eslava Barbara , van der Heijden E.P.A. , Jayakar Selwyn , Black Bryan James , Johnston Benjamin R. , Wainger Brian J. , Renthal William , Woolf Clifford J. , Eberlin Kyle R.
Published: October 2023

Neuromas are a substantial cause of morbidity and reduction in quality of life. This is not only caused by a disruption in motor and sensory function from the underlying nerve injury but also by the debilitating effects of neuropathic pain resulting from symptomatic neuromas. A wide range of surgical and therapeutic modalities have been introduced to mitigate this pain. Nevertheless, no single treatment option has been successful in completely resolving the associated constellation of symptoms. While certain novel surgical techniques have shown promising results in reducing neuroma-derived and phantom limb pain, their effectiveness and the exact mechanism behind their pain-relieving capacities have not yet been defined. Furthermore, surgery has inherent risks, may not be suitable for many patients, and may yet still fail to relieve pain. Therefore, there remains a great clinical need for additional therapeutic modalities to further improve treatment for patients with devastating injuries that lead to symptomatic neuromas. However, the molecular mechanisms and genetic contributions behind the regulatory programs that drive neuroma formation—as well as the resulting neuropathic pain—remain incompletely understood. Here, we review the histopathological features of symptomatic neuromas, our current understanding of the mechanisms that favor neuroma formation, and the putative contributory signals and regulatory programs that facilitate somatic pain, including neurotrophic factors, neuroinflammatory peptides, cytokines, along with transient receptor potential, and ionotropic channels that suggest possible approaches and innovations to identify novel clinical therapeutics.
Machine learning study of the extended drug–target interaction network informed by pain related voltage-gated sodium channels
Authors: Chen Long , Jiang Jian , Dou Bozheng , Feng Hongsong , Liu Jie , Zhu Yueying , Zhang Bengong , Zhou Tianshou , Wei Guo-Wei
Published: October 2023

Pain is a significant global health issue, and the current treatment options for pain management have limitations in terms of effectiveness, side effects, and potential for addiction. There is a pressing need for improved pain treatments and the development of new drugs. Voltage-gated sodium channels, particularly Nav1.3, Nav1.7, Nav1.8, and Nav1.9, play a crucial role in neuronal excitability and are predominantly expressed in the peripheral nervous system. Targeting these channels may provide a means to treat pain while minimizing central and cardiac adverse effects. In this study, we construct protein–protein interaction (PPI) networks based on pain-related sodium channels and develop a corresponding drug–target interaction network to identify potential lead compounds for pain management. To ensure reliable machine learning predictions, we carefully select 111 inhibitor data sets from a pool of more than 1000 targets in the PPI network. We employ 3 distinct machine learning algorithms combined with advanced natural language processing (NLP)–based embeddings, specifically pretrained transformer and autoencoder representations. Through a systematic screening process, we evaluate the side effects and repurposing potential of more than 150,000 drug candidates targeting Nav1.7 and Nav1.8 sodium channels. In addition, we assess the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of these candidates to identify leads with near-optimal characteristics. Our strategy provides an innovative platform for the pharmacological development of pain treatments, offering the potential for improved efficacy and reduced side effects.
Measurement properties of health-related quality of life measures for people living with metastatic disease of the spine: a systematic review
Authors: Qiao Liang , Ding Xing , He Shaohui , Zhang Fan , Yu Wenlong , Zhang Luosheng , Chen Dingbang , Gao Xin , Chu Peilin , Yan Yinjie , Huang Quan , Yang Xinghai , Yin Mengchen
Published: October 2023

Purpose:

Patients with spinal metastases (SM) suffer from a significant quality of life (QoL) deterioration. The measurement of QoL has garnered significant attention. In this study, we aimed to investigate the frequency of QoL measurement, systematically appraise the measurement properties of identified instruments, and facilitate the effective selection of an appropriate QoL instrument for patients with SM.

Methods:

This systematic review adhered to the newly revised Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. The methodological quality of studies was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Measurement property results were assessed using the adapted criteria. Each measurement property was allocated a separate rating (excellent, good, fair, or poor). “Best evidence synthesis” was performed using COSMIN outcomes and the quality of findings.

Result:

Two hundred and nine publications were included, and 18 instruments were identified. ECOG, EuroQol-5D, SF-36, SOSGOQ, and EORTC-QLQ-C30 were the top five instruments used for patients with SM in published literature. The measurement properties evaluated included internal consistency (four instruments), reliability (three instruments), validity (five instruments), validity (nine measures), floor and ceiling effects (four instruments), responsiveness (four instruments), and interpretability (three measures). Based on the limited evidence, Brief Pain Inventory (BPI) had the best methodological quality.

Conclusions:

Owing to the limitation of BPI in assessment domains, we cannot fully support the use of BPI. For the lack of high-quality research, it is challenging to nominate a single appropriate measure. Additional studies needed to explore the evidence before a confirmatory decision is made.
Prediction of survival in patients with infected pancreatic necrosis: a prospective cohort study
Authors: Ning Caihong , Ouyang Hui , Shen Dingcheng , Sun Zefang , Liu Baiqi , Hong Xiaoyue , Lin Chiayan , Li Jiarong , Chen Lu , Li Xinying , Huang Gengwen
Published: October 2023

Background:

Infected pancreatic necrosis (IPN) is a severe complication of acute pancreatitis, with mortality rates ranging from 15% to 35%. However, limited studies exist to predict the survival of IPN patients and nomogram has never been built. This study aimed to identify predictors of mortality, estimate conditional survival (CS), and develop a CS nomogram and logistic regression nomogram for real-time prediction of survival in IPN patients.

Methods:

A prospective cohort study was performed in 335 IPN patients consecutively enrolled at a large Chinese tertiary hospital from January 2011 to December 2022. The random survival forest method was first employed to identify the most significant predictors and capture clinically relevant nonlinear threshold effects. Instantaneous death risk and CS was first utilized to reveal the dynamic changes in survival of IPN patients. A Cox model-based nomogram incorporating CS and a logistic regression-based nomogram were first developed and internally validated with a bootstrap method.

Results:

The random survival forest model identified seven foremost predictors of mortality, including number of organ failures, duration of organ failure, age, time from onset to first intervention, hemorrhage, bloodstream infection, and severity classification. Duration of organ failure, and time from onset to first intervention showed distinct thresholds and nonlinear relationships with mortality. Instantaneous death risk reduced progressively within the first 30 days, and CS analysis indicated gradual improvement in real-time survival since diagnosis, with 90-day survival rates gradually increasing from 0.778 to 0.838, 0.881, 0.974, and 0.992 after surviving 15, 30, 45, 60, and 75 days, respectively. After further variables selection using step regression, five predictors (age, number of organ failures, hemorrhage, time from onset to first intervention, and bloodstream infection) were utilized to construct both the CS nomogram and logistic regression nomogram, both of which demonstrated excellent performance with 1000 bootstrap.

Conclusion:

Number of organ failures, duration of organ failure, age, time from onset to first intervention, hemorrhage, bloodstream infection, and severity classification were the most crucial predictors of mortality of IPN patients. The CS nomogram and logistic regression nomogram constructed by these predictors could help clinicians to predict real-time survival and optimize clinical decisions.
Initial Response to Combination Therapies for Tinnitus: Lessons Learned From a Retrospective Analysis
Authors: Shin Seung-Ho , Byun Sung Wan , Lee Ho Yun
Published: October 2023

Objective

To investigate the initial reduction of tinnitus effects by combining common therapies applicable in general otology clinics and establishing optimal treatment strategies.

Study Design

Retrospective cohort study.

Setting

A tertiary university hospital.

Patients

Patients with nonpulsatile subjective tinnitus who visited the hospital between January and December 2022.

Intervention(s)

Combination therapies consisting of at least one of the directive counseling based on the neurophysiological model, hearing aids, medication, and/or neuromodulation were performed.

Main Outcome Measure(s)

Tinnitus Handicap Inventory (THI) questionnaire at both their initial visit and 1-month follow-up.

Results

A total of 151 patients were enrolled. THI improvement of 20 points or more was observed in 31.8% of participants. One-way analysis of variance revealed that counseling had a significant reduction in THI, whereas neuromodulation, medication, and hearing aids did not. THI improvement was significantly associated with received counseling, severity of initial THI, and mean loudness discomfort level. Hearing aids and neuromodulation were not significant prognostic factors for improvement.

Conclusion

Counseling alone is the best treatment for most patients with tinnitus. There will be other patients with tinnitus that, in addition to counseling, would benefit from hearing aids, medications, and/or certain forms of neuromodulation.
Association of Smoke and Nicotine Product Consumption With Sensorineural Hearing Loss: A Population-Level Analysis
Authors: Li Marwin , Perlov Natalie M. , Patel Jena , Amin Dev , Kumar Ayan , Urdang Zachary D. , Willcox Thomas O. , Chiffer Rebecca C.
Published: October 2023

Objective

To test the hypothesis that use of cigarettes or other products with either cigarette-like smoke profile or high nicotine content by young populations increases the odds of developing sensorineural hearing loss (SNHL).

Study Design

Retrospective cohort study.

Setting

TriNetX US Collaborative Network (2003–2022).

Patients

Approximately 3.6 million patients at least 18 years old.

Intervention

None.

Main Outcome Measures

The primary outcome of interest was diagnosis of SNHL, defined using medical billing codes (International Classification of Diseases, Tenth Revision, Current Procedural Terminology, etc.). Cohort inclusion criteria included electronic health record entry after 2003, age 18 to 54 or 55+ years at index, and status of cigarette, noncigarette nicotine, or cannabis use. Covariates were controlled via 1:1 propensity score matching for SNHL-related conditions, including diabetes mellitus and ischemic diseases. Odds for developing SNHL were calculated against control subjects aged 18 to 54 years who have no record of nicotine/cannabis use.

Results

Odds for developing SNHL are higher for people 18 to 54 years old who use any nicotine product (odds ratio [95% confidence interval], 5.91 [5.71–6.13]), cigarettes only (4.00 [3.69–4.33]), chewing tobacco only (9.04 [7.09–11.63]), or cannabis only (3.99 [3.60–4.44]) compared with control. People 55+ years old who use no products also showed increased odds for SNHL (4.73 [4.63–4.85]).

Conclusions

Both nicotine and smoke exposure seem to be strongly associated with increased odds for developing SNHL, with chewing tobacco having the strongest association.
Characteristics and Management of Facial Nerve Schwannomas and Hemangiomas
Authors: Dandinarasaiah Manjunath , Grinblat Golda , Keshavamurthy Venkatesha Belur , Di Rubbo Vittoria M. , Alessandra Russo , Lauda Lorenzo , Sanna Mario
Published: October 2023

Objectives

To characterize facial nerve (FN) schwannomas (FNSs) and FN hemangiomas (FNHs) and their clinical features and management strategies, and to describe the results of cable nerve grafting after FN sectioning during tumor removal.

Methods

This retrospective study included 84 FNS cases and 42 FNH cases managed between July 1989 and July 2020 at a quaternary referral center for skull base pathology. Clinical details, locations, management, and results of cable nerve grafting at 1 year and during an average period of 3.12 years were evaluated. Sural nerve interpositioning was performed for patients who experienced FN paralysis for less than 1 year and underwent nerve sectioning during tumor removal.

Results

FNSs more often involved multiple segments compared with FNHs. The cerebellopontine angle and the mastoid segments were involved in 16 (19.1%) and 34 (40.5%) FNS cases, respectively; however, the cerebellopontine angle and the mastoid segments were involved in 0 and 7 (16.7%) FNH cases, respectively. Sectioned nerves of 99 patients (78.6%) were restored using interposition cable grafting. At the last follow-up evaluation, 56.3% of FNSs and 60.7% of FNHs attained House–Brackmann (HB) grade III. Lower preoperative HB grades were associated with poorer postoperative outcomes. For FNSs, the mean HB grades were 4.13 at 1 year postoperatively and 3.75 at the last follow-up evaluation (p = 0.001); however, for FNHs, the mean HB grades were 4.04 postoperatively and 3.75 at the last follow-up evaluation. Therefore, extradural coaptation yielded better outcomes.

Conclusion

FNSs can occur along any part of the FN along its course, and FNHs are concentrated around the area of geniculate ganglion. The results of cable inter positioning grafts are better in patients with preoperative FN-HB-III or less when compared with higher grades. The outcome of the interpositioning continues to improve even after 1 year in extradural coaptation.
Identification of Risk Factors for Mortality and Prolonged Hospitalization in Patients Treated With Surgical Drainage for Otogenic Intracranial Complications: A Nationwide Study Using a Japanese Inpatient Database
Authors: Hidaka Hiroshi , Tarasawa Kunio , Fujimori Kenji , Obara Taku , Fushimi Kiyohide , Shimamura Akihiro , Iwai Hiroshi
Published: October 2023

Objective

Data on risk factors for otogenic intracranial complications including cerebral abscess have been limited. Using a nationwide database, the aim was to identify the factors related to mortality and delayed discharge.

Study Design

Retrospective.

Setting

Nationwide database using the Diagnostic Procedure Combination database.

Main Outcome Measures

Data of 145 patients were extracted from a Japanese inpatient database between 2012 and 2020. The main outcome was survival at discharge. In a subgroup analysis of the 137 surviving patients, the second outcome was delayed discharge.

Results

The mortality rate was 5.5% (8 of 145). Logistic regression analyses identified intracerebral complications (adjusted odds ratio [OR], 3.09) and more than 2-day delay of the first surgery after admission (adjusted OR, 4.68) as risk factors for mortality. Specifically, consciousness level evaluated by the Japan Coma Scale (JCS) was significantly related to prolonged hospitalization or mortality: JCS I (adjusted OR, 3.40) and JCS ≥II (adjusted OR, 25.1).

Conclusions

Although otogenic intracranial complications are rare, and their mortality is decreasing because of the progress in imaging and clinical strategies, they remain the most severe complications of suppurative otitis media and/or cholesteatoma. Consciousness level at admission, comorbid diabetes mellitus, and a greater than 2-day delay of surgical intervention were related to prolonged hospitalization or mortality.
The management of severe traumatic brain injury in the initial postinjury hours – current evidence and controversies
Authors: Hossain Iftakher , Rostami Elham , Marklund Niklas
Published: October 2023

Purpose of review

To provide an overview of recent studies discussing novel strategies, controversies, and challenges in the management of severe traumatic brain injury (sTBI) in the initial postinjury hours.

Recent findings

Prehospital management of sTBI should adhere to Advanced Trauma Life Support (ATLS) principles. Maintaining oxygen saturation and blood pressure within target ranges on-scene by anesthetist, emergency physician or trained paramedics has resulted in improved outcomes. Emergency department (ED) management prioritizes airway control, stable blood pressure, spinal immobilization, and correction of impaired coagulation. Noninvasive techniques such as optic nerve sheath diameter measurement, pupillometry, and transcranial Doppler may aid in detecting intracranial hypertension. Osmotherapy and hyperventilation are effective as temporary measures to reduce intracranial pressure (ICP). Emergent computed tomography (CT) findings guide surgical interventions such as decompressive craniectomy, or evacuation of mass lesions. There are no neuroprotective drugs with proven clinical benefit, and steroids and hypothermia cannot be recommended due to adverse effects in randomized controlled trials.

Advancement of the prehospital and ED care that include stabilization of physiological parameters, rapid correction of impaired coagulation, noninvasive techniques to identify raised ICP, emergent surgical evacuation of mass lesions and/or decompressive craniectomy, and temporary measures to counteract increased ICP play pivotal roles in the initial management of sTBI. Individualized approaches considering the underlying pathology are crucial for accurate outcome prediction.
Maternal and fetal outcomes of acute pancreatitis in pregnancy: a population-based study
Authors: Niu Chengu , Zhang Jing , Liu Hongli , Zhu Kaiwen , Okolo Patrick I.
Published: October 2023

Background

Acute pancreatitis during pregnancy can have negative effects on both the mother and the fetus. The primary aim of this study is to evaluate the trends, maternal and fetal outcomes, and associated comorbidities of acute pancreatitis during pregnancy using data from the USA National Inpatient Sample (NIS) database.

Methods

This study is a retrospective analysis of hospital discharge records from the NIS database from 2009 to 2019.

Results

Delivery patients with acute pancreatitis faced a higher risk of maternal mortality (AOR 91.02, 95% CI 28.47–291.06), postpartum hemorrhage (AOR 1.59, 95% CI 1.02–2.49), and hypertensive complications (defined as preeclampsia, eclampsia, or HELLP syndrome) (AOR 3.42, 95% CI 2.56–4.56) compared to those without acute pancreatitis. Moreover, we saw an increased incidence of preterm labor (AOR 3.94, 95% CI 3.02–5.12) and fetal death (AOR 3.12, 95% CI 1.76–5.53). Rates of fetal restriction and large fetal size were comparable. Additionally, the acute pancreatitis group showed higher rates of acute kidney injury (4.2% vs. 0.06%; AOR, 31.02, 95% CI 12.50–76.98), severe sepsis (0.8% vs. 0.01%; AOR, 34.49, 95% CI 7.67–155.14), and respiratory failure (2.4% vs. 0.06%; AOR, 20.77, 95% CI (8.55–50.41). There were no significant differences in maternal and perinatal outcomes in biliary pancreatitis after the intervention compared to conservative treatment.

Conclusion

Acute pancreatitis during pregnancy can have negative effects on both the mother and fetus. Treatment for biliary pancreatitis does not affect maternal and fetal outcomes. An interdisciplinary approach is essential to ensure optimal outcomes for mothers and their offspring in these cases.
The correlation between serum 25-hydroxyvitamin D level and ulcerative colitis: a systematic review and meta-analysis
Authors: Liu Chenyu , Liu Xin , Shi Haitao , Chen Fenrong , Sun Linlang , Gao Xin , Wang Yan
Published: October 2023

Objective

The incidence of UC has increased yearly. Many studies have suggested that patients with ulcerative colitis have abnormal vitamin D levels. A systematic review and meta-analysis were conducted to investigate the association between vitamin D levels and ulcerative colitis.

Methods

We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database (VIP) from inception to December 2022. We included case-control studies comparing the differences in vitamin D levels between patients with ulcerative colitis and healthy populations. Meta-analysis was performed using Review Manager5.4, Stata17.0 and other software.

Results

Sixteen eligible observational studies were selected from 473 articles involving 2234 subjects, and they included 987 patients with ulcerative colitis and 1247 controls. The results showed that the serum level of vitamin D in patients with ulcerative colitis was significantly lower than that in healthy controls (SMD = −0.83, 95% CI: −1.18, −0.48). Vitamin D deficiency was reported in five studies. The prevalence of vitamin D deficiency was significantly higher in the ulcerative colitis group than in the healthy control group (OR = 1.90, 95% CI: 1.38, 2.62).

Conclusion

Serum vitamin D levels were significantly lower in patients with ulcerative colitis than in healthy controls.
Exploring Clinical Practice Hours in Postbaccalaureate-to-Doctor of Nursing Practice Nurse Practitioner Programs
Authors: Stager Sharon L. , Mitchell Sheryl , Bigley Mary Beth , Kelly-Weeder Susan , Fogg Louis
Published: October 2023

Background:

Advanced practice nursing education is evolving to the doctor of nursing practice (DNP) degree. The American Association of Colleges of Nursing (AACN) DNP Essentials required 1000 hours of direct patient care, whereas the Report of the National Task Force on Quality Nurse Practitioner Education (NTF) Criteria for Evaluation of Nurse Practitioner Programs required 500 direct patient care hours. Indirect hours were unclear and undefined. The AACN Essentials changed the 1000-hour requirement to 500 practice hours, and the NTF increased the direct patient care hours to 750.

Purpose:

The study sought to describe the distribution of direct and indirect hours that the National Organization of Nurse Practitioner Faculties member schools offer in their seamless postbaccalaureate-to-DNP nurse practitioner (NP) program.

Method:

A quantitative survey was distributed to schools of nursing.

Results:

Eighty-six surveys represented 86 distinct schools and 112 NP programs. Supervised direct patient care hours were an average of 791.31 hours. Indirect hours averaged 170.08 hours. The DNP project hours served as an indirect hour activity.

Conclusion:

Many schools have more than 750 direct hours adhering to the 2022 NTF Standards. The indirect hour allocation varies and weighs heavily on the DNP project.
Variable Adjustment Methods for Hemihamate Autograft Arthroplasty in Proximal Interphalangeal Joint Fracture/Dislocations
Authors: Heo Jae-Woo , Whang Jong Ick , Park Hyun Sik
Published: October 2023

Proximal interphalangeal joint fracture/dislocations, even after surgical correction, often lead to long-term complications including posttraumatic arthritis, prolonged joint stiffness, and chronic joint instability. A wide range of surgical techniques has been devised to resolve this issue, but none has been promising enough. Despite this circumstance, arthroplasty using a hemihamate autograft of size and contour that match the middle phalangeal base has progressed into one of more acceptable methods that provide both articular congruency and osseous stability. In this article, we introduce various types of proximal interphalangeal joint fracture/dislocations and individualized surgical approach using hemihamate autograft and lag screw and/or hook plate as fixation methods.
Associations between natural sunlight exposure and brain structural markers: a prospective study in the UK Biobank
Authors: Li Huihui , Cui Fusheng , Wang Tong , Wang Weijing , Zhang Dongfeng
Published: October 2023

Objective

Sunlight is closely intertwined with daily life. It remains unclear whether there are associations between sunlight exposure and brain structural markers.

Methods

This longitudinal study utilized baseline data (2006-2010) and follow-up data (2014+) from the UK Biobank. General linear regression analysis was employed to compare the differences in brain structural markers among different sunlight exposure time groups. Stratification analyses were performed based on sex, age, and diseases (hypertension, stroke, diabetes). Limiting cubic splines were performed to examine the dose-response relationship between natural sunlight exposure and brain structural markers, with further stratification by season. To control environmental and genetic factor, we adjusted PM2.5 and PRS for Alzheimer’s disease.

Results

A total of 27,474 participants were included in the final analyses. The association of sunlight exposure time with brain structural markers was found in the upper quartile compared to the lower quartile. Prolonged natural sunlight exposure was associated with the volumes of total brain (β: -0.051, P < 0.001), white matter (β: -0.031, P = 0.023), gray matter (β: -0.067, P < 0.001), and white matter hyperintensities (β: 0.059, P < 0.001). These associations were more pronounced in males and individuals under the age of 60. With daily sunlight exposure approximately exceeding 2 hours, we observed that total brain volume and gray matter volume decreased, while white matter high hyperintensity volume increased with prolonged sunlight exposure duration.

Conclusions

This study demonstrates that prolonged exposure to natural sunlight is associated with brain structural markers change. These findings offer new insights into the mechanisms underlying the association between natural sunlight and brain health.
A General Single-Cell Analysis Framework via Conditional Diffusion Generative Models
Authors: Tang Wenzhuo , Liu Renming , Wen Hongzhi , Dai Xinnan , Ding Jiayuan , Li Hang , Fan Wenqi , Xie Yuying , Tang Jiliang
Published: October 2023

Abstract

The fast-growing single-cell analysis community extends the horizon of quantitative analysis to numerous computational tasks. While the tasks hold vastly different targets from each other, existing works typically design specific model frameworks according to the downstream objectives. In this work, we propose a general single-cell analysis framework by unifying common computational tasks as posterior estimation problems. In light of conditional diffusion generative models, we introducescDiffthrough the proposed framework and study different conditioning strategies. With data-specific conditions,scDiffachieves competitive performance against state-of-the-art in various benchmarking tasks. In addition, we illustrate the flexibility ofscDiffby incorporating prior information through large language models and graph neural networks. Additional few-shot and zero-shot experiments prove the effectiveness of the prior conditioner onscDiff. Our implementation is publicly available athttps://github.com/OmicsML/scDiff.
Single-cell and Spatial Transcriptomics Clustering with an Optimized Adaptive K-Nearest Neighbor Graph
Authors: Li Jia , Shyr Yu , Liu Qi
Published: October 2023

Single-cell and spatial transcriptomics have been widely used to characterize cellular landscape in complex tissues. To understand cellular heterogeneity, one essential step is to define cell types through unsupervised clustering. While typical clustering methods have difficulty in identifying rare cell types, approaches specifically tailored to detect rare cell types gain their ability at the cost of poorer performance for grouping abundant ones. Here, we developed aKNNO, a method to identify abundant and rare cell types simultaneously based on an adaptive k-nearest neighbor graph with optimization. Benchmarked on 38 simulated and 20 single-cell and spatial transcriptomics datasets, aKNNO identified both abundant and rare cell types accurately. Without sacrificing performance for clustering abundant cell types, aKNNO discovered known and novel rare cell types that those typical and even specifically tailored methods failed to detect. aKNNO, using transcriptome alone, stereotyped fine-grained anatomical structures more precisely than those integrative approaches combining expression with spatial locations and histology image.
Evaluating the patterning cascade model of tooth morphogenesis in the human lower mixed and permanent dentition
Authors: Kenessey Dori E. , Stojanowski Christopher M. , Paul Kathleen S.
Published: October 2023

Objective

The patterning cascade model of crown morphogenesis has been studied extensively in a variety of organisms to elucidate the evolutionary history surrounding postcanine tooth form. The current research examines the degree to which model expectations are reflected in the crown configuration of lower deciduous and permanent molars in a modern human sample. This study has two main goals: 1) to determine if metameric and antimeric pairs significantly differ in size, accessory trait expression, and relative intercusp spacing, and 2) to establish if the relative distance among early-forming cusps accounts for observed variation in accessory cusp expression.

Methods

Tooth size, intercusp distance, and morphological trait expression data were collected from 3D scans of mandibular dental casts representing 124 individual participants of the Harvard Solomon Islands Project. Paired tests were utilized to compare tooth size, accessory trait expression, and relative intercusp distance between diphyodont metameres and permanent antimeres. Proportional odds logistic regression was implemented to investigate how the likelihood of accessory cusp formation varies as a function of the distance between early-developing cusps.

Results/Significance

For paired molars, results indicated significant discrepancies in tooth size and cusp 5 expression, but not cusp 6 and cusp 7 expression. Several relative intercusp distances emerged as important predictors of accessory cusp expression. These findings support previous quantitative genetic results and suggest the development of neighboring crown structures represents a zero-sum partitioning of cellular territory and resources. As such, this study contributes to a better understanding of the evolution of deciduous and permanent molar crown configuration in humans.
Two complementary circuits for spatial navigation in mouse: evidence from Fos mapping
Authors: Balcerek Edyta , Włodkowska Urszula , Czajkowski Rafał
Published: October 2023

We designed and implemented a novel spatial behavioral protocol based on the figure 8 maze paradigm. This solution employs a fully automated closed-loop system using visual contexts for guiding behavior. It allows high throughput testing of large cohorts of animals. This automated approach highly reduces the effect of stress, but also eliminates the influence of rule learning and the involvement of working memory. Here, we show that training mice in the apparatus leads to change in strategy from internal tendency to alternate into navigation based exclusively on visual cues. This effect could be achieved using two different protocols: prolonged alternation training, or a flexible protocol with unpredictable turn succession. We provide evidence of opposing levels of engagement of hippocampus and retrosplenial cortex after training mice in these two different regimens. This supports the hypothesis of the existence of parallel circuits supporting navigation, one based on the well described hippocampal representation, and another, RSC-dependent.
Clinically relevant humanized mouse models of metastatic prostate cancer to evaluate cancer therapies
Authors: Kostlan Raymond J. , Phoenix John T. , Budreika Audris , Ferrari Marina G. , Khurana Neetika , Cho Jae Eun , Juckette Kristin , McCollum Brooke L. , Moskal Russell , Mannan Rahul , Qiao Yuanyuan , Vander Griend Donald J. , Chinnaiyan Arul M. , Kregel Steven
Published: October 2023

There is tremendous need for improved prostate cancer (PCa) models. The mouse prostate does not spontaneously form tumors and is anatomically and developmentally different from the human prostate. Engineered mouse models lack the heterogeneity of human cancer and rarely establish metastatic growth. Human xenografts represent an alternative but rely on an immunocompromised host. Accordingly, we generated PCa murine xenograft models with an intact human immune system (huNOG and huNOG-EXL mice) to test whether humanizing tumor-immune interactions would improve modeling of metastatic PCa and the impact of hormonal and immunotherapies. These mice maintain multiple human cell lineages, including functional human T-cells and myeloid cells. In 22Rv1 xenografts, subcutaneous tumor size was not significantly altered across conditions; however, metastasis to secondary sites differed in castrate huNOG vs background-matched immunocompromised mice treated with enzalutamide (enza). VCaP xenograft tumors showed decreases in growth with enza and anti-Programed-Death-1 treatments in huNOG mice, and no effect was seen with treatment in NOG mice. Enza responses in huNOG and NOG mice were distinct and associated with increased T-cells within tumors of enza treated huNOG mice, and increased T-cell activation. In huNOG-EXL mice, which support human myeloid development, there was a strong population of immunosuppressive regulatory T-cells and Myeloid-Derived-Suppressor-Cells (MDSCs), and enza treatment showed no difference in metastasis. Results illustrate, to our knowledge, the first model of human PCa that metastasizes to clinically relevant locations, has an intact human immune system, responds appropriately to standard-of-care hormonal therapies, and can model both an immunosuppressive and checkpoint-inhibition responsive immune microenvironment.
The chromatin accessibility dynamics during cell fate specifications in zebrafish early embryogenesis
Authors: Xu Qiushi , Zhang Yunlong , Xu Wei , Liu Dong , Jin Wenfei , Chen Xi , Hong Ni
Published: October 2023

Chromatin accessibility plays a critical role in the regulation of cell fate decisions. Although gene expression changes have been extensively profiled at the single-cell level during early embryogenesis, the dynamics of chromatin accessibility atcis-regulatory elements remain poorly studied. Here, we used a plate-based single-cell ATAC-seq method to profile the chromatin accessibility dynamics of over 10, 000 nuclei from zebrafish embryos. We investigated several important time points immediately after zygotic genome activation (ZGA), covering key developmental stages up to dome. The results revealed key chromatin signatures in the first cell fate specifications when cells start to differentiate into enveloping layer (EVL) and yolk syncytial layer (YSL) cells. Finally, we uncovered many potential cell-type specific enhancers and transcription factor motifs that are important for the cell fate specifications.