bluuebunny/crossref_metadata_2025 huggingface dataset:
Percutaneous endoscopic lumbar discectomy for L5-S1 disc herniation based on image analysis and clinical findings: A retrospective review of 345 cases
Authors: Shen Shih-Chieh , Chen Hung-Chieh , Tsou Hsi-Kai , Lin Ruei-Hong , Shih Yu-Tung , Huang Chih-Wei , Tang Chien-Lun , Chen Hsien-Te , Chang Chien-Chun , Tzeng Chung-Yuh
Published: February 2023

The effect of spinal anatomical anomalies on the efficacy of percutaneous endoscopic lumbar discectomy (PELD) for disc herniation repair is unclear. This retrospective review aims to assess the safety and effectiveness of PELD for treating L5-S1 disc herniation with a range of characteristics and to determine the prevalence of lumbosacral transitional vertebrae (LSTV) anatomical anomalies to facilitate pre-surgical planning. From July 2005 to June 2019, 345 patients with L5-S1 disc herniations were treated with PELD. The primary outcome was 1-year postoperative visual analogue scale scores for low back and lower limb pain. The secondary outcomes included the surgical approach used, lumbosacral bony anomalies, presence of a ruptured disc or severely calcified disc, pediatric lumbar disc herniation, recurrent disc herniation management, and the long-term outcome. visual analogue scale scores for most patients were significantly improved after surgery. The prevalence of LSTVs was 4.05% (14/345 patients) in lumbar sacralization and 7.53% (26/345 patients) in sacral lumbarization. The prevalence of ruptured and severely calcified discs was 18.55% (64/345) and 5.79% (20/345), respectively. The prevalence of pediatric lumbar disc herniation was 2.02% (7/345). The recurrence rate was 4.34% (15/345). Two durotomy cases without sequelae and 8 cases of lower limb dysesthesia lasting longer than 3 months postoperatively were reported. PELD is safe and effective for treating L5-S1 disc herniation, including cases complicated by calcified lumbar disc herniation, disc rupture with migration, and the presence of LSTV. Appropriate imaging is essential to identify case-specific factors, including the prevalent LSTV anatomical anomalies, before surgery.
Pharmaceutical care of rituximab in the treatment of children with refractory anti-NMDAR encephalitis: A case report
Authors: Wu Haiyan , Xu Xiaoyan , Ding Qixuan , Zhu Shuangfei , Zheng Qiaozhen , Ding Shanshan , Li Jiyao , Zhao Hongyang
Published: February 2023

Rationale:

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare disease of nervous system, which is mediated by autoimmune mechanisms. The treatment of anti-NMDAR encephalitis includes Immunotherapy, symptomatic and supportive treatment for seizures and psychiatric symptoms. There are many kinds of drugs, so drug treatment management and pharmaceutical care for children are particularly important. At present, there are few reports on pharmaceutical care for children with this disease. Clinical pharmacists participated in the pharmaceutical care of a child with refractory anti-NMDAR encephalitis treated with rituximab, conducted drug treatment management on the dosage, administration method, complications and other aspects of off-label use of rituximab, combined with the children’s clinical manifestations, inflammatory indicators, pathogenic detection, blood concentration, liver and kidney functions, drug interactions and other factors. The treatment plan of anti-infective drugs shall be adjusted, and attention shall be paid to whether there are adverse reactions during the treatment.

Patient concerns:

A 4-year-old girl presented with epileptic seizure, intermittent recurrent fever, high inflammatory markers, abnormal psychiatric function/cognitive impairment, language disorder, consciousness disturbance, and movement disorder/involuntary movement.

Diagnosis:

Refractory anti-NMDAR encephalitis.

Interventions:

The patient was given first-line (3 rounds of methylprednisolone pulse therapy and gamma globulin) and second-line (rituximab) immunotherapy. On the advice of a clinical pharmacist, the patient wasn’t given Advanced antibacterial agents (voriconazole, vancomycin) therapy. On the 41st day of admission, the patient’s temperature and inflammatory indicators were normal, CD19+ B cells were reduced to 0.

Outcomes:

The patient consciousness level, cognition and orientation were gradually improved, mental disorder was improved, involuntary movement was obviously controlled, no seizure occurred again, and the patient was discharged with stable condition.

Lessons:

Clinical pharmacists ensure the safety, effectiveness and economy of patients’ medication by carrying out the whole process of individualized drug treatment management and care for patients.
Comparison of ultrasound-guided radiofrequency ablation and hepatectomy for colorectal liver metastasis: A protocol for systematic review and meta-analysis
Authors: Wu Lianming , Xu Weiwei , Hu Yanzi , Chen Jing
Published: February 2023

Background:

Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors. Surgical treatment has made great progress in CRC liver metastasis (CRLM), including radiofrequency ablation (RFA), and hepatectomy. We perform a protocol for systematic review and meta-analysis to compare the efficacy and safety of ultrasound-guided RFA and hepatectomy in treating CRLM.

Methods:

This systematic review protocol will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) 2015 Statement. The protocol has been registered in PROSPERO (CRD42022371561). PubMed, EMBASE, MEDLINE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, ClinicalTrials.gov trials registry, and Chinese Clinical Trial Registry will be searched from January 1980 to December 2022. Only randomized controlled trials will be included. Cochrane systematic evaluation tool is used to assess the risk of bias. The RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) will be applied to conduct the meta-analyses.

Results:

The results of this systematic review and meta-analysis will be publicly available and published in a peer-reviewed journal.

Conclusion:

This study may provide more convincing evidence to help surgeons make decisions when dealing with CRLM.
Integrated Pathologic Score Effectively Stratifies Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreaticoduodenectomy
Authors: Sohn Aaron J. , Taherian Mehran , Katz Matthew H.G. , Prakash Laura R. , Chatterjee Deyali , Wang Hua , Kim Michael , Tzeng Ching-Wei D. , Lee Jeffrey E. , Ikoma Naruhiko , Rashid Asif , Wolff Robert A. , Zhao Dan , Koay Eugene J. , Sun Ryan , Maitra Anirban , Wang Huamin
Published: February 2023

Neoadjuvant therapy is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Pathologic parameters of treated PDAC, including tumor (ypT) and lymph node (ypN) stage, and tumor response grading (TRG) are important prognostic factors in this group of patients. To our knowledge, a multifactorial prognostic score combining pathologic features including ypT, ypN, and TRG in treated PDAC patients has not been reported. Our cohort consisted of 398 PDAC patients who received neoadjuvant therapy and underwent pancreaticoduodenectomy at our institution. All pancreaticoduodenectomy specimens were grossly and microscopically evaluated using a standard protocol. The integrated pathologic score (IPS) was calculated as the sum of the scores for ypT, ypN, and TRG according to either the MD Anderson grading system (IPSMDA) or the College of American Pathologists (CAP) grading system (IPSCAP). The IPSMDA and IPSCAP were correlated with clinicopathologic parameters and patient survival. Using either IPSMDA or IPSCAP, PDAC patients were stratified into 3 distinct prognostic groups for both disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001). The IPSMDA and IPSCAP correlated with tumor differentiation, margin status, the American Joint Committee on Cancer (AJCC) stage, and tumor recurrence (P<0.05). In multivariate analysis, IPSMDA, IPSCAP, margin status, and tumor differentiation were independent prognostic factors for both DFS (P<0.05) and OS (P<0.05). However, patients with AJCC stage IB, IIA, or IIB disease had no significant difference in either DFS or OS (P>0.05). The IPS appears to provide improved prognostic information compared with AJCC staging for preoperatively treated patients with PDAC.
Improved survival for severely injured patients receiving massive transfusion at US teaching hospitals: A nationwide analysis
Authors: Ramsey Walter A. , O'Neil Christopher F. , Fils Aaron J. , Botero-Fonnegra Cristina , Saberi Rebecca A. , Gilna Gareth P. , Pizano Louis R. , Parker Brandon M. , Proctor Kenneth G. , Schulman Carl I. , Namias Nicholas , Meizoso Jonathan P.
Published: February 2023

BACKGROUND

Previous studies have shown improved survival for patients treated at American College of Surgeons (ACS)–verified level I trauma centers compared with level II, level III, and undesignated centers. This mortality difference is more pronounced in severely injured patients. However, a survival benefit for severely injured trauma patients has not been established at teaching institutions compared with nonteaching centers. Because massive transfusion (MT) is associated with high mortality, we hypothesize that patients receiving MT have lower mortality at teaching hospitals than at nonteaching hospitals.

METHODS

All adult ACS Trauma Quality Improvement Program–eligible patients who underwent MT, defined as >10 U of packed red blood cells in the first 4 hours after arrival, in the 2019 ACS Trauma Quality Programs participant use file were eligible. Patients with severe head injury (head Abbreviated Injury Scale score, ≥3), prehospital cardiac arrest, and interhospital transfers were excluded. Logistic regression models were used to assess the effects of trauma center hospital teaching status on the adjusted odds of 3-hour, 6-hour, and 24-hour mortality.

RESULTS

A total of 1,849 patients received MT (81% male; median Injury Severity Score, 26 [18–35]), 72% were admitted to level I trauma centers, and 28% were admitted to level II centers. Overall hospital mortality was 41%; 17% of patients died in 3 hours, 25% in 6 hours, and 33% in 24 hours. Teaching hospitals were associated with decreased 3-hour (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.27–0.75), 6-hour (OR, 0.37; 95% CI, 0.24–0.56), 24-hour (OR, 0.50; 95% CI, 0.34–0.75), and overall mortality (OR, 0.66; 95% CI, 0.44–0.98), compared with nonteaching hospitals, controlling for sex, age, heart rate, injury severity, injury mechanism, and trauma center verification level.

CONCLUSION

Severely injured patients requiring MT experience significantly lower mortality at teaching hospitals compared with nonteaching hospitals, independently of trauma center verification level.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
In Vivo Regeneration of Tubular Small Intestine With Motility: A Novel Approach by Orthotopic Transplantation of Decellularized Scaffold
Authors: Kojima Hidenobu , Ishii Takamichi , Fukumitsu Ken , Ogiso Satoshi , Tomofuji Katsuhiro , Oshima Yu , Horie Hiroshi , Ito Takashi , Wakama Satoshi , Makino Kenta , Hatano Etsuro
Published: February 2023

Background.

Whole-intestine engineering can provide a therapeutic alternative to bowel transplantation. Intestinal components including the mucosa, muscular layer, enteric nervous system, and vasculature must be reestablished as a tubular organ to generate an artificial small intestine. This study proposes a novel approach to produce a transplantable, well-organized tubular small intestine using a decellularized scaffold.

Methods.

Male Lewis rat intestines were used to generate decellularized scaffolds. Patch or tubular grafts were prepared from the decellularized intestine and transplanted into the rat intestine orthotopically. Histological analysis of the decellularized intestine was performed up to 12 wk after transplantation.

Results.

Histological examination revealed abundant vascularization into the decellularized patch graft 1 wk after transplantation. Muscular and nervous components, as well as cryptogenesis, were observed in the decellularized patch graft 2 wk after transplantation. Sixteen of the 18 rats survived with normal intake of food and water after the decellularized tubular graft transplantation. Compared with silicone tube grafts, the decellularized tubular grafts significantly promoted the infiltration and growth of intestinal components including the mucosa, muscular layer, and nerve plexus from the recipients. Circular and longitudinal muscle with a well-developed myenteric plexus was regenerated, and intestinal motility was confirmed in the decellularized tubular graft 12 wk after transplantation.

Conclusions.

Orthotopic transplantation of decellularized intestine enhanced the reconstruction of the well-organized tubular small intestine with an enteric nervous system in vivo. Our method using a decellularized scaffold represents a promising approach toward whole-intestine engineering and provides a therapeutic alternative for the irreversible intestinal failure.
Three novel Actinoplanes species isolated by using polyaspartic acid as a water-retaining agent for the enrichment in situ
Authors: Ding La-mei , Ding Pei-zhi , Liu Wen-long , Shen Hong-ling , Xia Zhan-feng , Wan Chuan-Xing , Zhang Li-li
Published: February 2023

Three novel actinomycete strains, designated TRM66264-DLMT, TRM88002T and TRM88003T, were isolated by using polyaspartic acid as a water-retaining agent for the enrichment in situ. The 16S rRNA gene sequence and phylogenetic analyses of three strains indicated that they belonged to the genus

Actinoplanes

. The phylogenetically closest strains of TRM66264-DLMT, TRM88002T and TRM88003T were

Actinoplanes bogorensis

LIPI11-2-Ac043T (98.4 %),

Actinoplanes abujensis

A4029T (98.0 %) and

Actinoplanes ferrugineus

IFO15555T (98.1 %), respectively. The major polar lipids of strains TRM66264-DLMT and TRM88002T were phosphatidylethanolamine and disphosphatidylglycerol, while strain TRM88003T only had phosphatidylethanolamine. The predominant menaquinones of strain TRM66264-DLMT were identified as MK-9(H4) and MK-9 (H6). Strains TRM88002T and TRM88003T had MK-9(H4). The cell-wall peptidoglycan of three strains contained meso-diaminopimelic acid. The whole-cell sugars of strain TRM66264-DLMT were identified as arabinose, glucose, galactose and xylose. Strains TRM88002T and TRM88003T mainly had arabinose and glucose. The DNA G+C content of strains TRM66264-DLMT, TRM88002T and TRM88003T were 70.48, 70.46 and 70.64 mol%, respectively. Genotypic and phenotypic analysis confirmed that all three strains sre new members of the genus Acinoplanes. Therefore, it is proposed that strains TRM66264-DLMT, TRM88002T and TRM88003T represent three novel species of the genus

Actinoplanes

, for which the names Actinoplanes polyasparticus sp. nov. (type strain TRM66264-DLMT=CCTCC AA 2021015T=LMG 32389T), Actinoplanes hotanensis sp. nov. (type strain TRM88002T=CCTCC AA 2021036T=LMG 32621T) and Actinoplanes aksuensis sp. nov. (type strain TRM88003T=CCTCC AA 2021037 T=LMG 32622T) are proposed.
Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference?
Authors: Diaz Perez Kimberly K. , Chung Sydney , Head S. Taylor , Epstein Michael P. , Hecht Jacqueline T. , Wehby George L. , Weinberg Seth M. , Murray Jeffrey C. , Marazita Mary L. , Leslie Elizabeth J.
Published: February 2023

Whole-exome sequencing (WES) is now a relatively straightforward process to identify causal variants in Mendelian disorders. However, the same is not true for WES in families where the inheritance patterns are less clear, and a complex etiology is suspected. Orofacial clefts (OFCs) are highly heritable birth defects with both Mendelian and complex etiologies. The phenotypic spectrum of OFCs may include overt clefts and several subclinical phenotypes, such as discontinuities in theorbicularis orismuscle (OOM) in the upper lip, velopharyngeal insufficiency (VPI), microform clefts or bifid uvulas. We hypothesize that expanding the OFC phenotype to include these phenotypes can clarify inheritance patterns in multiplex families, making them appear more Mendelian. We performed whole-exome sequencing to find rare, likely causal genetic variants in 31 multiplex OFC families, which included families with multiple individuals with OFCs and individuals with subclinical phenotypes. We identified likely causal variants inCOL11A2, IRF6, KLF4, SHROOM3, SMC3, TP63, andTBX3in seven families. Although we did not find clear evidence supporting the subclinical phenotype hypothesis, our findings support a role for rare variants in the etiology of OFCs.
Longitudinal and Quantitative Fecal Shedding Dynamics of SARS-CoV-2, Pepper Mild Mottle Virus and CrAssphage
Authors: Arts Peter J. , Kelly J. Daniel , Midgley Claire M. , Anglin Khamal , Lu Scott , Abedi Glen R. , Andino Raul , Bakker Kevin M. , Banman Bryon , Boehm Alexandria B. , Briggs-Hagen Melissa , Brouwer Andrew F. , Davidson Michelle C. , Eisenberg Marisa C. , Garcia-Knight Miguel , Knight Sterling , Peluso Michael J. , Pineda-Ramirez Jesus , Sanchez Ruth Diaz , Saydah Sharon , Tassetto Michel , Martin Jeffrey N. , Wigginton Krista R.
Published: February 2023

Wastewater-based epidemiology (WBE) emerged during the COVID-19 pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden, though the lack of high-quality, longitudinal fecal shedding data of SARS-CoV-2 and other viruses limits the interpretation and applicability of wastewater measurements. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as the commonly used fecal indicators Pepper Mild Mottle Virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2 infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding, with individual measurements varying from below limit of detection to 2.79×106gene copies/mg - dry mass of stool (gc/mg-dw). Of individuals that contributed at least 3 samples covering a range of at least 15 of the first 30 days after initial acute symptom onset, 77.4% had at least one positive SARS-CoV-2 RNA stool sample measurement. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall; and measured crAssphage DNA above detection limits in 80% (38/48) of individuals and 48% (179/371) of samples. Median shedding values for PMMoV and crAssphage nucleic acids were 1×105gc/mg-dw and 1.86×103gc/mg-dw, respectively. These results can be used to inform and build mechanistic models to significantly broaden the potential of WBE modeling and to provide more accurate insight into SARS-CoV-2 prevalence estimates.
The National Transportation Noise Exposure Map
Authors: Seto Edmund , Huang Ching-Hsuan
Published: February 2023

We describe the development and public availability of the National Transportation Noise Exposure Map with the goal of estimating population exposures to various noise levels at the census tract level in the United States. The map was created by overlaying the Bureau of Transportation Statistics’ National Transportation Noise Map with 5-year block group population estimates from the American Community Survey, and aggregating exposed population estimates to the census tract level. Based on the exposure map, an estimated 94.9 million people (29.1 % of the total U. S. population) were exposed to ≥ 45 dB LAeq of transportation-related noise, and approximately 11.9 million (3.6 %) were exposed to ≥ 60 dB in the year 2020.The exposure maps indicate that the greatest population proportion and number of individuals exposed were in California, while generally the map illustrates high proportions of exposure for populations living along major U. S. roadways and in airport communities. The availability of this new exposure map will facilitate the integration of noise exposures into a variety of studies, including regional and national health impact assessments, epidemiologic, and environmental justice studies.
Evaluating ChatGPT as an Adjunct for Radiologic Decision-Making
Authors: Rao Arya , Kim John , Kamineni Meghana , Pang Michael , Lie Winston , Succi Marc D.
Published: February 2023

BACKGROUND

ChatGPT, a popular new large language model (LLM) built by OpenAI, has shown impressive performance in a number of specialized applications. Despite the rising popularity and performance of AI, studies evaluating the use of LLMs for clinical decision support are lacking.

PURPOSE

To evaluate ChatGPT’s capacity for clinical decision support in radiology via the identification of appropriate imaging services for two important clinical presentations: breast cancer screening and breast pain.

MATERIALS AND METHODS

We compared ChatGPT’s responses to the American College of Radiology (ACR) Appropriateness Criteria for breast pain and breast cancer screening. Our prompt formats included an open-ended (OE) format, where ChatGPT was asked to provide the single most appropriate imaging procedure, and a select all that apply (SATA) format, where ChatGPT was given a list of imaging modalities to assess. Scoring criteria evaluated whether proposed imaging modalities were in accordance with ACR guidelines.

RESULTS

ChatGPT achieved an average OE score of 1.83 (out of 2) and a SATA average percentage correct of 88.9% for breast cancer screening prompts, and an average OE score of 1.125 (out of 2) and a SATA average percentage correct of 58.3% for breast pain prompts.

CONCLUSION

Our results demonstrate the feasibility of using ChatGPT for radiologic decision making, with the potential to improve clinical workflow and responsible use of radiology services.
A Machine Learning Approach to Predict Cellular Mechanical Stresses in Response to Chemical Perturbation
Authors: SubramanianBalachandar V.A. , Islam Md. Mydul , Steward R. L.
Published: February 2023

Mechanical stresses generated at the cell-cell level and cell-substrate level have been suggested to be important in a host of physiological and pathological processes. However, the influence various chemical compounds have on the mechanical stresses mentioned above is poorly understood, hindering the discovery of novel therapeutics and representing a barrier in the field. To overcome this barrier, we implemented two machine learning (ML) Models: Stepwise Linear Regression (SLR) and Quadratic Support Vector Machine (QSVM) to predict the dose-dependent response of tractions and intercellular stresses to chemical perturbation. We used traction and intercellular stress experimental data gathered from 0.2 μg/mL and 2 μg/mL drug concentrations along with cell morphological properties to train our model. To demonstrate the predictive capability of our ML model we predicted tractions and intercellular stresses in response to 0 μg/ml & 1 μg/ml drug concentrations. Results revealed the QSVM model to best predict intercellular stresses, while SLR best predicted tractions.

Author Summary

The ML framework we present here can be used to predict the mechanical response of any anchorage-dependent cell type to any chemical perturbation. The proposed ML can directly predict the intercellular stresses or tractions as a function of drug dosage and/or monolayer/cell coverage area which could potentially reduce the experimental time on studying the mechanics of cells to external chemicals or mechanical constraints. We believe our findings could be helpful in accelerating drug discovery and increase our understanding in the role of cellular stresses during disease progression.
A maize lipid droplet-associated protein is modulated by a virus to promote viral multiplication and infection
Authors: Wang Siyuan , Li Siqi , Wang Xinyu , Sun Xi , Xue Mingshuo , Di Dianping , Zhang Aihong , Zhang Yongjiang , Xia Yiji , Zhou Tao , Fan Zaifeng
Published: February 2023

Pathogen infection induces massive reprogramming of host primary metabolism. Lipid and fatty acid metabolism is generally disrupted by pathogens and co-opted for their proliferation. Lipid droplets (LDs) that play important roles in regulating cellular lipid metabolism are utilized by a variety of pathogens in mammalian cells. However, the function of LDs during pathogenic infection in plants remains unknown. We show here that infection by rice black streaked dwarf virus (RBSDV) affects the lipid metabolism of maize, which causes elevated accumulation of C18 polyunsaturated fatty acids (PUFAs) leading to viral proliferation and symptom development. Overexpression of one of the two novel LD-associated proteins (LDAPs) of maize (ZmLDAP1 and ZmLDAP2) induces LD clustering. The core capsid protein P8 of RBSDV interacts with ZmLDAP2 and prevents its degradation through the ubiquitin-proteasome system mediated by a UBX domain-containing protein, PUX10. In addition, silencing of theZmLDAP2down-regulates expression of fatty acid desaturase genes in maize, leading to a decrease in C18 PUFAs levels and suppression of RBSDV accumulation. Our findings reveal that the plant virus recruits LDAP to regulate cellular fatty acid metabolism to promote viral multiplication and infection. These results expand the knowledge of the LD functions and viral infection mechanism in plants.

One Sentence Summary

Rice black streaked dwarf virus recruits a lipid droplet-associated protein to regulate cellular fatty acid metabolism for promoting viral multiplication and infection.
Mental health outcomes of encephalitis: an international web-based study
Authors: Abdat Yasmin , Butler Matt , Zandi Michael , Michael Benedict D , Coutinho Ester , Nicholson Timothy R , Easton Ava , Pollak Thomas A
Published: February 2023

Encephalitis is associated with psychiatric symptoms in the acute and post-acute stages, and many survivors experience long-term sequelae. Despite this, the breadth and severity of mental health symptoms in survivors of encephalitis has not been systematically reported. We recruited adults who had been diagnosed with encephalitis of any aetiology to complete a web-based questionnaire assessing a wide range of mental health symptoms and disorders. In total, 445 respondents from 31 countries (55.1% UK, 23.1% USA, 2.2% low-and middle-income countries) completed the survey, with a median seven years since encephalitis diagnosis; 84.7% were diagnosed by a neurologist or infectious diseases doctor. Infectious encephalitis constituted 65.4% of cases, autoimmune 29.7%. Mean age was 50.1 years (SD 15.6); 65.8% were female. The most common self-reported psychiatric symptoms were anxiety (75.2%), sleep problems (64.4%), mood problems (62.2%), unexpected crying (35.2%), and aggression (29.9%). Rates of self-reported psychiatric diagnoses following encephalitis were high: anxiety (44.0%), depression (38.6%), panic disorder (15.7%), and post-traumatic stress disorder (PTSD, 21.3%); these rates were broadly consistent with the results of a validated self-report measure, the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Severe mental illnesses such as psychosis (3.3%) and bipolar affective disorder (3.1%) were also reported. Many respondents also felt they had symptoms of disorders including anxiety (37.5%), depression (28.1%), PTSD (26.8%), or panic disorder (20.9%) which had not been diagnosed by a professional. Overall, rates of major self-reported psychiatric diagnoses and symptoms did not significantly differ between autoimmune and infectious encephalitis. In total, 37.5% of respondents had thought about suicide, and 4.4% had attempted suicide since their encephalitis diagnosis. Over half (53.5%) reported that they either had no, or substandard, access to appropriate care for their mental health. High rates of sensory hypersensitivities (>75%) suggest a previously unreported association between encephalitis and this distressing symptom cluster. This large international survey indicates that psychiatric symptoms following encephalitis are common, and that mental healthcare provision to this population may be inadequate, highlighting a need for increased provision of proactive psychiatric care for these patients.
Prediction of Preeclampsia from Clinical and Genetic Risk Factors in Early and Late Pregnancy Using Machine Learning and Polygenic Risk Scores
Authors: Kovacheva Vesela P , Eberhard Braden W , Cohen Raphael Y , Maher Matthew , Saxena Richa , Gray Kathryn J
Published: February 2023

Background

Preeclampsia, a pregnancy-specific condition associated with new-onset hypertension after 20 weeks gestation, is a leading cause of maternal and neonatal morbidity and mortality. Predictive tools to understand which individuals are most at risk are needed.

Methods

We identified a cohort of N=1,125 pregnant individuals who delivered between 05/2015-05/2022 at Mass General Brigham hospitals with available electronic health record (EHR) data and linked genetic data. Using clinical EHR data and systolic blood pressure polygenic risk scores (SBP PRS) derived from a large genome-wide association study, we developed machine learning (xgboost) and linear regression models to predict preeclampsia risk.

Results

Pregnant individuals with an SBP PRS in the top quartile had higher blood pressures throughout pregnancy compared to patients within the lowest quartile SBP PRS. In the first trimester, the most predictive model was xgboost, with an area under the curve (AUC) of 0.73. Adding the SBP PRS to the models improved the performance only of the linear regression model from AUC 0.70 to 0.71; the predictive power of other models remained unchanged. In late pregnancy, with data obtained up to the delivery admission, the best performing model was xgboost using clinical variables, which achieved an AUC of 0.91.

Conclusions

Integrating clinical and genetic factors into predictive models can inform personalized preeclampsia risk and achieve higher predictive power than the current practice. In the future, personalized tools can be implemented in clinical practice to identify high-risk patients for preventative therapies and timely intervention to improve adverse maternal and neonatal outcomes.
Increased Spatiotemporal Variability after Stroke is not Just the Outcome of Walking Velocity
Authors: Koren Yogev , Barzel Oren , Shmuelof Lior , Handelzalts Shirley
Published: February 2023

Background

Increased spatiotemporal gait variability is considered a clinical biomarker of ageing and pathology, and a predictor of future falls. Nevertheless, it is unclear whether the increased spatiotemporal variability observed in persons with stroke (PwS) is directly related to the pathology or simply reflects their choice of walking velocity.

Research question

Does increased spatiotemporal gait variability directly relate to motor coordination deficits after stroke?

Methods

Forty PwS and 20 healthy adults participated in this cross-sectional study. Participants performed the lower-extremity motor coordination test (LEMOCOT) on an electronic mat equipped with force sensors. Then, participants walked for 120 s over a computerized treadmill at their comfortable walking velocity. For the LEMOCOT we used the traditional score of in-target touch count and computed the absolute and variable error around the targets. For gait variability, we extracted the standard deviation of step time, step length, step velocity, and step width. Using a data-based approach, we generated a model of the relationship between velocity and variability and tested the correlations of the velocity-controlled values with the outcome measures from the LEMOCOT.

Results

PwS demonstrated increased variability in step time, step length, and step velocity, as well as decreased variability in step width, in comparison to healthy adults, even after controlling for walking velocity. After controlling for walking velocity, we observed that for PwS the LEMOCOT score correlated with the variance in step time, and the variable error in the LEMOCOT correlated with the variance in step length, in step width, and in step velocity. No significant correlation with any of the velocity-controlled step parameters was found for the absolute error in the LEMOCOT.

Significance

Decreased performance in the LEMOCOT was associated with increased spatiotemporal variability in PwS, regardless of their walking velocity. Our results demonstrate the connection between lower-extremity coordination impairments and deficits in gait function.
Anticipating and assessing adverse and other unintended consequences of public health interventions: the (CONSEQUENT) framework
Authors: Stratil Jan M , Biallas Renke L , Movsisyan Ani , Oliver Kathryn , Rehfuess Eva A
Published: February 2023

1

Despite the best intentions public health interventions (PHIs) can have adverse and other unintended consequences (AUCs). AUCs are rarely systematically examined when developing, evaluating or implementing PHIs. We used a structured, multi-pronged and evidence-based approach to develop a framework to support researchers and decision-makers in conceptualising and categorising AUCs of PHIs.

We employed the ‘best-fit’ framework synthesis approach. We designed the a-priori framework using elements of the WHO-INTEGRATE framework and the Behaviour Change Wheel. Next, we conducted a qualitative systematic review of theoretical and conceptual publications on the AUCs of PHIs in the databases Medline and Embase as well as through grey literature searches. Based on these findings, we iteratively revised and advanced the a-priori framework based on thematic analysis of the identified research. To validate and further refine the framework, we coded four systematic reviews on AUCs of distinct PHIs against it.

The CONSEQUENT framework includes two components: the first focuses on AUCs and serves to categorise them; the second component highlights the mechanisms through which AUCs may arise. The first component comprises eight domains of consequences – health, health system, human and fundamental rights, acceptability and adherence, equality and equity, social and institutional, economic and resource, and ecological.

The CONSEQUENT framework is intended to facilitate conceptualisation and categorising of AUCs of PHIs during their development, evaluation and implementation to support evidence-informed decision-making.
Trends in cross-border and illicit tobacco purchases and associations with motivation to stop smoking and quit attempts: a representative survey of smokers in England, 2019-2022
Authors: Jackson Sarah E. , Cox Sharon , Brown Jamie
Published: February 2023

Objectives

The last five years have seen substantial changes in England’s social and economic landscape as a result of Brexit, the Covid-19 pandemic, and cost-of-living crisis. We aimed to examine changes in cross-border and illicit tobacco purchasing, and associations with quitting activity, over this period.

Design

Nationally-representative monthly cross-sectional survey.

Setting

England, 2019-2022.

Participants

11,232 adult (≥18y) past-year smokers.

Main outcome measures

We estimated time trends in the proportion of smokers reporting purchasing tobacco from (i) cross-border and (ii) illicit sources in the past 6 months, and examined associations with motivation to stop smoking (among current smokers) and past-year quit attempts (among past-year smokers).

Results

Between February 2019 and October 2022, there was a non-linear increase in the proportion of smokers reporting purchasing cross-border tobacco (from 5.2% to 16.1%; PR=3.10, 95%CI=2.03-4.73) but no overall change in the proportion reporting purchasing illicit tobacco (from 9.2% to 8.5%; PR=0.92, 95%CI=0.70-1.21). Both cross-border (ORadj=0.65, 95%CI=0.56-0.77) and illicit (ORadj=0.74, 95%CI=0.63-0.86) tobacco purchasing were associated with lower odds of reporting a recent quit attempt. Smokers who purchased cross-border tobacco also reported lower motivation to stop smoking (ORadj=0.84, 95%CI=0.75-0.95).

Conclusions

Despite a fall in cross-border tobacco purchasing during the first year of the Covid-19 pandemic, the proportion of smokers in England reporting purchasing cross-border tobacco is now three times higher than it was at the start of 2019. The proportion reporting purchasing illicit tobacco has not changed substantially. Tackling the increasing use of cheap tobacco in England may be an important target for motivating quit attempts.

What this paper adds

What is already known on this topic

Tobacco tax avoidance and evasion strategies, such as buying tobacco cheaply from cross-border or illicit sources, undermine the effectiveness of tax policy.

What this study adds

Since February 2019, the proportion of smokers in England reporting purchasing cross-border tobacco has tripled, while the proportion reporting purchasing illicit tobacco remains similar. Smokers who use cheap tobacco are less likely to try to quit.

How this study might affect research, practice or policy

Policy measures that reduce smokers’ access to these cheaper sources of tobacco could help to increase the rate of quit attempts among smokers and accelerate progress toward the government’s smokefree 2030 target.
Effect of Total Sphingomyelin Synthase Activity on Low Density Lipoprotein Catabolism in Mice
Authors: Li Zhiqiang , He Mulin , Chen Guangzhi , Worgall Tilla S. , Jiang Xian-Cheng
Published: February 2023

Background

Sphingomyelin (SM) and cholesterol are two key lipid partners on cell membranes and on lipoproteins. Many studies have indicated the influence of cholesterol on SM metabolism. This study examined the influence of SM biosynthesis on cholesterol metabolism.

Methods

Inducible globalSms1KO/globalSms2KO mice were prepared to evaluate the effect of whole-body SM biosynthesis deficiency on lipoprotein metabolism. Tissue cholesterol, SM, ceramide, and glucosylceramide levels were measured. TG production rate and LDL catabolism were measured. Lipid rafts were isolated and LDL receptor mass and function were evaluated. Also, the effects of exogenous sphingolipids on hepatocytes were investigated.

Results

We found that total SMS depletion significantly reduced plasma SM levels. Also, the total deficiency significantly induced plasma cholesterol, apoB, and apoE levels. Importantly, total SMS deficiency, but not SMS2 deficiency, dramatically decreased LDL receptors in the liver and attenuated LDL uptake through the receptor. Further, we found that total SMS deficiency greatly reduced LDL receptors in the lipid rafts which contained significantly lower SM and significantly higher glucosylceramide as well as cholesterol. Furthermore, we treated primary hepatocytes and Huh7 cells (a human hepatoma cell line) with SM, ceramide, or glucosylceramide, and we found that only SM could up-regulate LDL receptor levels in a dose-dependent fashion.

Conclusions

Whole-body SM biosynthesis plays an important role in LDL-cholesterol catabolism. The total SMS deficiency, but not SMS2 deficiency, reduces LDL uptake and causes LDL-cholesterol accumulation in the circulation. Given the fact that serum SM level is a risk factor for cardiovascular diseases, inhibiting SMS2 but not SMS1 should be the desirable approach.

Graphic Abstract
Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies
Authors: Painter Mark M. , Johnston Timothy S. , Lundgreen Kendall A. , Santos Jefferson J.S. , Qin Juliana S. , Goel Rishi R. , Apostolidis Sokratis A. , Mathew Divij , Fulmer Bria , Williams Justine C. , McKeague Michelle L. , Pattekar Ajinkya , Goode Ahmad , Nasta Sean , Baxter Amy E. , Giles Josephine R. , Skelly Ashwin N. , Felley Laura E. , McLaughlin Maura , Weaver Joellen ,   Penn Medicine BioBank, Kuthuru Oliva , Dougherty Jeanette , Adamski Sharon , Long Sherea , Kee Macy , Clendenin Cynthia , da Silva Antunes Ricardo , Grifoni Alba , Weiskopf Daniela , Sette Alessandro , Huang Alexander C. , Rader Daniel J. , Hensley Scott E. , Bates Paul , Greenplate Allison R. , Wherry E. John
Published: February 2023

SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.
Automatic Whole Body FDG PET/CT Lesion Segmentation using Residual UNet and Adaptive Ensemble
Authors: Murugesan Gowtham Krishnan , McCrumb Diana , Brunner Eric , Kumar Jithendra , Soni Rahul , Grigorash Vasily , Chang Anthony , VanOss Jeff , Moore Stephen
Published: February 2023

Multimodal Positron Emission Tomography/Computed Tomography (PET/CT) plays a key role in the diagnosis, staging, restaging, treatment response assessment, and radiotherapy planning of malignant tumors. The complementary nature of high-resolution anatomic CT and high sensitivity/specificity molecular PET imaging provides accurate assessment of disease status [14] In oncology, 18-fluorodeoxyglucose (FDG) PET/CT is the most widely used method to identify and analyze metabolically active tumors. In particular, FDG uptake allows for more accurate detection of both nodal and distant forms of metastatic disease. Accurate quantification and staging of tumors is the most important prognostic factor for predicting the survival of patients and for designing personalized patient management plans. [8,3] Analyzing PET/CT quantitatively by experienced medical imaging experts/radiologists is timeconsuming and error-prone. Automated quantitative analysis by deep learning algorithms to segment tumor lesions will enable accurate feature extraction, tumor staging, radiotherapy planning, and treatment response assessment. The AutoPET Challenge 2022 provided an opensource platform to develop and benchmark deep learning models for automated PET lesion segmentation by providing large open-source wholebody FDG-PET/CT data. Using the multimodal PET/CT data from 900 subjects with 1014 studies provided by the AutoPET MICCAI 2022 Challenge, we applied fivefold cross-validation on residual UNETs to automatically segment lesions. We then utilized the output from adaptive ensemble highly contributive models as the final segmentation. Our method achieved a 10th ranking with a dice score of 0.5541 in the heldout test dataset (N=150 studies).
Intraoral thermal processing in the gustatory cortex of awake mice
Authors: Bouaichi Cecilia G. , Odegaard Katherine E. , Neese Camden , Vincis Roberto
Published: February 2023

Oral temperature is a sensory cue relevant to food preference and nutrition. To understand how orally-sourced thermal inputs are represented in the gustatory cortex (GC) we recorded neural responses from the GC of male and female mice presented with deionized water at different innocuous temperatures (14 °C, 25 °C, 36 °C) and taste stimuli (room temperature). Our results demonstrate that GC neurons encode orally-sourced thermal information in the absence of classical taste qualities at the single neuron and population levels, as confirmed through additional experiments comparing GC neuron responses to water and artificial saliva. Analysis of thermal-evoked responses showed broadly tuned neurons that responded to temperature in a mostly monotonic manner. Spatial location may play a minor role regarding thermosensory activity; aside from the most ventral GC, neurons reliably responded to and encoded thermal information across the dorso-ventral and antero-postero cortical axes. Additional analysis revealed that more than half of GC neurons that encoded chemosensory taste stimuli also accurately discriminated thermal information, providing additional evidence of the GC’s involvement in processing thermosensory information important for ingestive behaviors. In terms of convergence, we found that GC neurons encoding information about both taste and temperature were broadly tuned and carried more information than taste-selective only neurons; both groups encoded similar information about the palatability of stimuli. Altogether, our data reveal new details of the cortical code for the mammalian intraoral thermosensory system in behaving mice and pave the way for future investigations on GC functions and operational principles with respect to thermogustation.
Image-guided deployment and monitoring of a novel tungsten nanoparticle–infused radiopaque absorbable inferior vena cava filter in pigs
Authors: San Valentin Erin Marie , Damasco Jossana A. , Bernardino Marvin , Court Karem A. , Godin Biana , Canlas Gino Martin , Melancon Adam , Chintalapani Gouthami , Jacobsen Megan C. , Norton William , Layman Rick R. , Fowlkes Natalie , Chen Stephen R. , Huang Steven Y. , Melancon Marites P.
Published: February 2023

The use of absorbable inferior vena cava filters (IVCFs) constructed with poly-p-dioxanone (PPDO) eliminates risks and complications associated with the use of retrievable metallic filters. Radiopacity of radiolucent PPDO IVCFs can be improved with the incorporation of nanoparticles (NPs) made of high-atomic number materials such as gold and bismuth. In this study, we focused on incorporating tungsten NPs (WNPs), along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of the WNPs. We compared the imaging properties of WNPs with single-polymer PHB (W-P) and WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB). Ourin vitroanalyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the inherent physico-mechanical properties of the PPDO sutures. We observed a more sustained release of WNPs from W-PB-coated sutures than W-P-coated sutures. We successfully deployed W-P- and W-PB-coated IVCFs into the inferior vena cava of pig models, with monitoring by fluoroscopy. At the time of deployment, W-PB-coated IVCFs showed a 2-fold increase in radiopacity compared to W-P-coated IVCFs. Longitudinal monitoring ofin vivoIVCFs over a 12-week period showed a drastic decrease in radiopacity at week 3 for both filters. Results of this study highlight the utility of NPs and polymers for enhancing radiopacity of medical devices; however, different methods of incorporating NPs and polymers can still be explored to improve the efficacy, safety, and quality of absorbable IVCFs.