bluuebunny/crossref_metadata_2025 huggingface dataset:
Fascia Lata: Another Workhorse for Complex Skull Base Reconstruction
Authors: Godse Neal R. , Sreenath Satyan B. , Sbeih Firas , Woodard Troy D. , Kshettry Varun R. , Recinos Pablo F. , Sindwani Raj
Published: April 2023

Background

Multiple methods exist for skull base reconstruction of defects created by expanded endonasal approaches. While the nasoseptal flap (NSF) has been well established as the workhorse of mucosal reconstruction in complex skull base defects in multi-layered closures, a variety of options exist for the inner layer of multilayer reconstruction, including fascia lata (FL).

Objective

To present our experience and outcomes in utilizing FL in multiple ways to reconstruct a wide variety of complex skull base defects.

Methods

Retrospective review was performed from May 2017 to February 2022 to identify 50 consecutive patients who underwent endoscopic skull base reconstruction using FL.

Results

FL was employed for reconstruction in 50 patients included in the study: 37 undergoing primary expanded endonasal skull base surgery and 13 revision cases. A wide range of complex pathology was treated, with meningioma and craniopharyngioma being the two most common. FL was utilized as a “button” graft (34/50, 68.0%), free graft inlay/onlay (13/50, 26.0%), and as a button graft combined with onlay (3/50, 6.0%). Expanded surgery defects addressed included tuberculum sella/sphenoid planum (36/50, 72.0%), clivus (6/50, 12.0%), and cribriform/planum (8/50, 16.0%). Successful reconstruction with fascia lata was accomplished in 46/50 cases (92%), with only 4 cases (8%) requiring revision for post-op CSF leak. Donor-site complications were rare with only 1 case (2.0%) of post-op seroma.

Conclusion

FL, usually with NSF, offers a versatile option for the reconstruction of challenging defects with excellent outcomes and minimal morbidity. FL is emerging as a workhorse for reconstruction of the inner layer of complex skull base defects.
Epidermis-on-a-chip system to develop skin barrier and melanin mimicking model
Authors: Li Qiwei , Wang Chunyan , Li Xiaoran , Zhang Jing , Zhang Zilin , Yang Keyu , Ouyang Jun , Zha Shaohui , Sha Lifeng , Ge Jianjun , Chen Zaozao , Gu Zhongze
Published: April 2023

In vitro skin models are rapidly developing and have been widely used in various fields as an alternative to traditional animal experiments. However, most traditional static skin models are constructed on Transwell plates without a dynamic three-dimensional (3D) culture microenvironment. Compared with native human and animal skin, such in vitro skin models are not completely biomimetic, especially regarding their thickness and permeability. Therefore, there is an urgent need to develop an automated biomimetic human microphysiological system (MPS), which can be used to construct in vitro skin models and improve bionic performance. In this work, we describe the development of a triple-well microfluidic-based epidermis-on-a-chip (EoC) system, possessing epidermis barrier and melanin-mimicking functions, as well as being semi-solid specimen friendly. The special design of our EoC system allows pasty and semi-solid substances to be effectively utilized in testing, as well as allowing for long-term culturing and imaging. The epidermis in this EoC system is well-differentiated, including basal, spinous, granular, and cornified layers with appropriate epidermis marker (e.g. keratin-10, keratin-14, involucrin, loricrin, and filaggrin) expression levels in corresponding layers. We further demonstrate that this organotypic chip can prevent permeation of over 99.83% of cascade blue (a 607 Da fluorescent molecule), and prednisone acetate (PA) was applied to test percutaneous penetration in the EoC. Finally, we tested the whitening effect of a cosmetic on the proposed EoC, thus demonstrating its efficacy. In summary, we developed a biomimetic EoC system for epidermis recreation, which could potentially serve as a useful tool for skin irritation, permeability, cosmetic evaluation, and drug safety tests.
Acute partial papillary muscle rupture as a rare complication following non-ST elevation myocardial infarction
Authors: Asllanaj Blerina , Farr Matthew , McWhorter Yi
Published: April 2023

Papillary muscle rupture is a life-threatening complication of acute myocardial infarction that most commonly occurs 2–7 days after the infarct. We present a rare case of acute partial anterolateral papillary muscle rupture following non-ST elevation myocardial infarction. Our patient was an elderly male who had a detached anterolateral papillary muscle, which required emergent mitral valve replacement. Papillary muscle rupture is a rare complication of acute myocardial infarction, and anterolateral muscle rupture occurs even less commonly. When papillary muscle rupture is diagnosed, patients need to be emergently referred to cardiothoracic surgery as mortality without surgery is over 90% within a week.
Extrapolation and AI transparency: Why machine learning models should reveal when they make decisions beyond their training
Authors: Cao Xuenan , Yousefzadeh Roozbeh
Published: April 2023

The right to artificial intelligence (AI) explainability has consolidated as a consensus in the research community and policy-making. However, a key component of explainability has been missing: extrapolation, which can reveal whether a model is making inferences beyond the boundaries of its training. We report that AI models extrapolate outside their range of familiar data, frequently and without notifying the users and stakeholders. Knowing whether a model has extrapolated or not is a fundamental insight that should be included in explaining AI models in favor of transparency, accountability, and fairness. Instead of dwelling on the negatives, we offer ways to clear the roadblocks in promoting AI transparency. Our commentary accompanies practical clauses useful to include in AI regulations such as the AI Bill of Rights, the National AI Initiative Act in the United States, and the AI Act by the European Commission.
Improving adherence and health outcomes in testicular cancer survivors using a mobile health-based intervention: A mixed-methods pilot study
Authors: Deleemans Julie M , Samnani Sunil , Lloyd Chris , Alimohamed Nimira
Published: April 2023

Objective

Testicular cancer (TC) is one of the most common cancers among young men, with survival rates exceeding 97% due to effective treatments. Post-treatment follow-up care is important for long-term survival and monitoring psychosocial symptoms, yet TC survivors (TCS) show poor adherence to post-treatment care. Mobile-health-based interventions show high acceptability in men with cancer. This study will examine the feasibility of using the Zamplo health app to improve adherence to post-treatment care and support psychosocial outcomes in TCS.

Methods

This mixed-methods, longitudinal, single-arm pilot study will recruit N = 30 patients with a diagnosis of TC who finished treatment within ≤ 6 months and are currently aged ≥18 years old. Adherence to follow-up appointments (e.g. blood work, scans) will be assessed (primary outcome), and measures for fatigue, depression, anxiety, sexual satisfaction and function, social roles satisfaction, general mental and physical health and body image (secondary outcomes) will be completed at four-time points: baseline, 3, 6 and 12 months. One-on-one semi-structured interviews will be conducted post-intervention (month 12).

Results

Improvements in post-treatment follow-up appointment adherence and psychosocial outcomes will be analyzed using descriptive statistics, paired samples t-tests to determine changes across time points 1 through 4, and correlation analysis. Qualitative data will be analyzed using thematic analysis.

Conclusion

Findings will inform future, larger trials that incorporate evaluation of sustainability and economic implications to improve adherence to TC follow-up guidelines. Findings will be disseminated via infographics, social media, publications and presentations conducted in partnership with TC support organizations and at conferences.
An Analysis of COVID-19 Mortality During the Dominancy of Alpha, Delta, and Omicron in the USA
Authors: Tabatabai Mohammad , Juarez Paul D. , Matthews-Juarez Patricia , Wilus Derek M. , Ramesh Aramandla , Alcendor Donald J. , Tabatabai Niki , Singh Karan P.
Published: April 2023

Background:

The objective of the study was to measure the risk of death due to COVID-19 in relation to individuals’ characteristics, and severity of their disease during the dominant periods of Alpha, Delta, and Omicron variants have influenced mortality rates.

Methods:

This study was conducted using COVID-19 Centers for Disease Control and Prevention (CDC) Case Surveillance Public Data Taskforce for 57 states, and United States territories between January 1, 2020 and March 20, 2022. Multivariable binary Hyperbolastic regression of type I was used to analyzes the data.

Results:

Seniors and ICU-admitted patients had the highest risk of death. For each additional percent increase in fully vaccinated individuals, the odds of death deceased by 1%. The odds of death prior to vaccine availability, compared to post vaccine availability, was 1.27. When comparing the time periods each variant was dominant, the odds of death was 3.45-fold higher during Delta compared to Alpha. All predictor variables had P-values ≤.001.

Conclusion:

There was a noticeable difference in the odds of death among subcategories of age, race/ethnicity, sex, PMCs, hospitalization, ICU, vaccine availability, variant, and percent of fully vaccinated individuals.
Poverty Alleviation Efficiency of Tourism and Its Spatiotemporal Differentiation in Jiangxi Province of China Based on the DEA Model
Authors: Xiao Kun , Ullah Wahid , Fu Jiaqi , Zhang Xinmin
Published: April 2023

Based on the DEA model, this paper evaluates the efficiency of poverty alleviation through tourism in Jiangxi Province based on three aspects: comprehensive efficiency, technical efficiency, and scale efficiency. The results show that the overall efficiency of poverty alleviation through tourism in Jiangxi Province is gradually progressing toward a high level, with the average value in recent years reaching 0.765. Compared to other cities in the Province, Ganzhou and Fuzhou have the highest ranking by level of tourism poverty alleviation. However, the tourism development at present is not truly just or even, resulting in a gap between the efficiency levels of regions. There are some areas that have been in the effective state for a long time, while others are far lower than the average efficiency due to low technical efficiency in these areas. The spatial differentiation of tourism poverty alleviation efficiency across regions shows that the tourism poverty alleviation efficiency in the eastern region of Jiangxi Province is low compared to other parts. Although the overall efficiency of tourism poverty alleviation in Jiangxi Province does not fluctuate much, there are still some areas where the efficiency of tourism poverty alleviation continues to show a downward trend, indicating that the allocation of tourism resources in Jiangxi Province needs to be optimized and leaving much room for improvement in the efficiency of poverty alleviation.
Spondylodiscitis in Geriatric Patients: What Are the Issues?
Authors: Herren Christian , von der Hoeh Nicolas Heinz , Zwingenberger Stefan , Sauer Daniel , Jung Norma , Pieroh Philipp , Drange Steffen , Pumberger Matthias , Scheyerer Max J. ,   and Spine Section of the German Society for Orthopaedics and Trauma
Published: April 2023

Study Design

Review article.

Objectives

A review of literature on the treatment of pyogenic spondylodiscitis in geriatric patients was performed with the aim to give an overview about these special patients and a recommendation on necessary diagnostics as well as conservative and operative treatment options.

Methods

A systematic computerized literature search was done by the spondylodiscitis working group of the German Society for Orthopedics and Trauma Surgery.

Results

Spondylodiscitis has an increasing incidence by age with a peak at 75 years or older. The 1-year mortality without an appropriate treatment is with 15 to 20% extremely high. Pathogen detection is the essential diagnostic step and the basis for a sufficient antibiotic treatment. Geriatric patients have initially less elevated inflammatory parameters. Compared to younger patients. They have a longer length of hospital stay and take longer for CRP normalization. Even the outcome between conservative and operative treatment is comparable after one year. Patients with spinal instability, immobilizing pain, epidural abscess, and newly emerged neurological deficits should be considered for operative treatment.

Conclusions

The treatment of geriatric patients with pyogenic spondylodiscitis must take into account that these patients usually have multiple comorbidities. The main goals are resistance-based antibiotics and the shortest possible time of immobilization of the patient.
Combined Odontoid (C2) and Atlas (C1) Fractures in Geriatric Patients: A Systematic Review and Treatment Recommendation
Authors: Spiegl Ulrich J. A. , Keil Holger , Krause Johannes , Osterhoff Georg , Scheyerer Max J. , Schnake Klaus John , Perl Mario
Published: April 2023

Study Design

Systematic review.

Objective

The aim of this study was to conduct a systematic overview of the pathogenesis and the treatment options of combined odontoid and atlas fractures in geriatric patients.

Methods

This review is based on articles retrieved by a systematic search in the PubMed and Web of Science databases for articles published until February 2021 dealing with combination fractures of C1 and C2 in geriatric patients.

Results

Altogether, 438 articles were retrieved from the literature search. A total of 430 articles were excluded. The remaining eight original articles were included in this systematic review depicting the topics pathogenesis, non-operative treatment, posterior approach, and anterior approach. The overall level of evidence of the studies is low.

Conclusion

Combined odontoid and atlas fractures in the geriatric population are commonly caused by simple falls and seem to be associated with atlanto-odontoid osteoarthritis. Non-operative treatment with a cervical orthosis is a feasible treatment option in the majority of patients with stable C2 fractures. In case of surgery posterior C1 and C 2 stabilization and anterior triple or quadruple screw fixation are possible techniques. Some patients may also deserve an occipito-cervical fusion. A possible treatment algorithm is proposed.
Treatment and Outcome of Osteoporotic Thoracolumbar Vertebral Fractures With Anterior or Posterior Tension Band Failure (OF 5): Short-Term Results From the Prospective EOFTT Multicenter Study
Authors: Osterhoff Georg , Schenk Philipp , Katscher Sebastian , Schnake Klaus John , Bäumlein Martin , Zimmermann Volker , Schmeiser Gregor , Scherer Michael A. , Müller Michael , Sprengel Kai , Liepold Katja , Schramm Simon , Baron Christopher , Siekmann Holger , Schwarz Falko , Franck Alexander , Scheyerer Max J. , Spiegl Ulrich J. A. , Ullrich Bernhard W. ,   Working Group Osteoporotic Fractures of the Spine Section of the German Society of Orthopaedics and Trauma
Published: April 2023

Study Design

Subgroup analysis of a multicenter prospective cohort study

Objective

To analyse surgical strategies applied to osteoporotic thoracolumbar osteoporotic fracture (OF) 5 injuries with anterior or posterior tension band failure and to assess related complications and clinical outcome.

Methods

A multicenter prospective cohort study (EOFTT) was conducted at 17 spine centers including 518 consecutive patients who were treated for an osteoporotic vertebral fracture (OVF). For the present study, only patients with OF 5 fractures were analysed. Outcome parameters were complications, Visual Analogue Scale (VAS), Oswestry Disability Questionnaire (ODI), Timed Up & Go test (TUG), EQ-5D 5L, and Barthel Index.

Results

In total, 19 patients (78 ± 7 years, 13 female) were analysed. Operative treatment consisted of long-segment posterior instrumentation in 9 cases and short-segment posterior instrumentation in 10 cases. Pedicle screws were augmented in 68 %, augmentation of the fractured vertebra was performed in 42%, and additional anterior reconstruction was done in 21 %. Two patients (11 %) received short-segment posterior instrumentation without either anterior reconstruction or cement-augmentation of the fractured vertebra. No surgical or major complications occurred, but general postoperative complications were observed in 45%. At a follow-up of mean 20 ± 10 weeks (range, 12 to 48 weeks), patients showed significant improvements in all functional outcome parameters.

Conclusions

In this analysis of patients with type OF 5 fractures, surgical stabilization was the treatment of choice and lead to significant short-term improvement in terms of functional outcome and quality of life despite a high general complication rate.
Avoiding Spinal Implant Failures in Osteoporotic Patients: A Narrative Review
Authors: Schömig Friederike , Becker Luis , Schönnagel Lukas , Völker Anna , Disch Alexander C. , Schnake Klaus John , Pumberger Matthias
Published: April 2023

Study design

Narrative review.

Objectives

With an aging population, the prevalence of osteoporosis is continuously rising. As osseous integrity is crucial for bony fusion and implant stability, previous studies have shown osteoporosis to be associated with an increased risk for implant failure and higher reoperation rates after spine surgery. Thus, our review’s purpose was to provide an update of evidence-based solutions in the surgical treatment of osteoporosis patients.

Methods

We summarize the existing literature regarding changes associated with decreased bone mineral density (BMD) and resulting biomechanical implications for the spine as well as multidisciplinary treatment strategies to avoid implant failures in osteoporotic patients.

Results

Osteoporosis is caused by an uncoupling of the bone remodeling cycle based on an unbalancing of bone resorption and formation and resulting reduced BMD. The reduction in trabecular structure, increased porosity of cancellous bone and decreased cross-linking between trabeculae cause a higher risk of complications after spinal implant-based surgeries. Thus, patients with osteoporosis require special planning considerations, including adequate preoperative evaluation and optimization. Surgical strategies aim towards maximizing screw pull-out strength, toggle resistance, as well as primary and secondary construct stability.

Conclusions

As osteoporosis plays a crucial role in the fate of patients undergoing spine surgery, surgeons need to be aware of the specific implications of low BMD. While there still is no consensus on the best course of treatment, multidisciplinary preoperative assessment and adherence to specific surgical principles help reduce the rate of implant-related complications.
An Investigation Into the Relationship Between the Sedimentation Sign and Lumbar Disc Herniation in Upright Magnetic Resonance Images
Authors: Patel Kishan , Son Seung Min , Zhang Qiwen , Wang Jeffrey C. , Buser Zorica
Published: April 2023

Study Design

Retrospective Upright MRI Study.

Objectives

Determine the relationship between lumbar disc herniation and presence of the nerve root sedimentation sign on upright kinematic MRI patients.

Methods

T2-weighted axial upright kMRI images of 100 patients with the presence of disc herniation in at least 1 lumbar disc between L1/L2 and L5/S1 were obtained. Sedimentation sign, spinal canal anterior-posterior (AP) diameter, disc height, disc herniation size, type of herniation, and zone of herniation were evaluated. A positive sedimentation sign was defined as having either the majority of nerve roots running ventrally or centrally in the canal or conglomeration of the nerve roots at the mid-disc level. Herniation types were defined as either no herniation, disc bulge, protrusion, extrusion, or sequestration. Zones of herniation were categorized as either central, lateral, or far lateral.

Results

The kappa value of intra-observer reliability was .915. The kappa value of disc levels with a negative sedimentation sign were seen more frequently (n = 326, 65.2%) than those with a positive sedimentation sign (n = 174, 34.8%). The spinal canal AP diameter was significantly decreased at the L3/L4 and L4/L5 level in patients with a positive sedimentation sign. Discs with a positive sedimentation sign had a larger average size of disc herniation compared to those with a negative sign at all levels. A relationship between positivity of the sedimentation sign and disc herniation type was significant at L2/L3, L3/L4, and L4/L5.

Conclusions

Patients with a positive sedimentation sign were seen to have larger disc herniations and more severely degenerated discs.
Development and Validation of an Islamic Investor’s Sentiment Scale for Stock Market Investment
Authors: Begam M. Rahila , Babu Manivannan , Sulphey M. M.
Published: April 2023

Islamic law prohibits Muslims from investing in certain businesses such as banking, alcohol, and speculation. As such, Islamic investment is different from traditional investment, as investment principles emphasize ethical investing and compliance with Shariah, the Islamic rule that controls every aspect of a Muslim’s life. However, a fair review of the literature failed to find any questionnaire to measure Islamic investor sentiment. In order to create and standardize a technique to gauge Islamic investors’ attitudes about share market investment, a research was conducted. Islamic investors’ attitudes were the dependent variable, while the study identified Islamic investing ethics, religious considerations, profitability, social impact, and information accessibility as independent variables. Python programming was used to evaluate the data gathered from 391 respondents using a 24-item structured questionnaire. According to the study’s findings, each of the characteristics has a big influence on how Islamic investors feel. Furthermore, this study shows that participation in religious activities elevates the spirits of Islamic investors. The verified Islamic investor’s feelings questionnaire in this study is expected to inspire more investigation in this fascinating field.
The Corticosteroid Meniscectomy Trial of Extended-Release Triamcinolone Injection After Arthroscopic Partial Meniscectomy: Protocol for a Double-Blind Randomized Controlled Trial
Authors: Sullivan James K. , Gottreich Julia R. , Huston Laura J. , Imrey Peter B. , Winalski Carl S. , Li Xiaojuan , Spindler Kurt P. , Tomko Patrick M. , Cox Charles L. , Wright Rick W. , Jones Morgan H.
Published: April 2023

Background:

Meniscal tear in older adults often accompanies knee osteoarthritis and is commonly treated with arthroscopic partial meniscectomy (APM) when patients have persistent pain after a trial of physical therapy. Cross-sectional evidence suggests that synovitis is associated with baseline pain in this patient population, but little is known about the relationship between synovitis and postoperative recovery or progression of knee osteoarthritis.

Purpose/Hypothesis:

Intra-articular extended-release triamcinolone may reduce inflammation and thereby improve outcomes and slow disease progression. This article presents the rationale behind the Corticosteroid Meniscectomy Trial (CoMeT) and describes its study design and implementation strategies.

Study Design:

Randomized controlled trial.

Methods:

CoMeT is a 2-arm, 3-center, randomized placebo-controlled trial designed to establish the clinical efficacy of extended-release triamcinolone administered via intra-articular injection immediately after APM. The primary outcome is change in Knee injury and Osteoarthritis Outcome Score Pain subscore at 3-month follow-up. Synovial biopsy, joint fluid aspirate, and urine and blood sample analyses will examine the associations between various objective measures of baseline inflammation and pre- and postoperative outcome measures and clinical responses to triamcinolone intervention. Quantitative 3-T magnetic resonance imaging will evaluate cartilage and meniscal composition and 3-dimensional bone shape to detect early joint degeneration.

Results:

We discuss methodologic innovations and challenges.

Conclusion:

To our knowledge, this is the first randomized double-blind clinical trial that will analyze the effect of extended-release triamcinolone acetonide on pain, magnetic resonance imaging measures of structural change and effusion/synovitis, soluble biomarkers, and synovial tissue transcriptomics after APM.
Be in the Digital Room Where it Happens, Part II: Social Media for Neurology Educators
Authors: Goldstein Jessica , Martindale Jaclyn M. , Albin Catherine , Xixis Kathryn , Gottlieb-Smith Rachel , Otallah Scott , Lakhotia Arpita , Strauss Lauren D. , Bass Nancy , Strowd Roy E. , Rodman Adam
Published: April 2023

Social media has changed the way we communicate and interact. Unsurprisingly, it has also changed how we teach and learn. Younger generations of learners have transitioned from traditional educational sources to digital ones. Medical educators need to adapt to trends in medical education and develop fluency in the digital methods used by medical learners today. This is part two of a two-part series on social media and digital education in neurology. This article provides an overview of how social media can be used as a teaching tool in medical education and provides an overview in which it is grounded. We offer practical strategies on how social media can promote lifelong learning, educator development, educator support, and foster educator identity with accompanying neurology-specific examples. We also review considerations for incorporating social media into teaching and learning practices and future directions for integrating these tools in neurology education.
Impact of COVID-19 on Dental Care Utilization and Oral Health Conditions in the United States
Authors: Choi S.E. , Mo E. , Sima C. , Wu H. , Thakkar-Samtani M. , Tranby E.P. , Frantsve-Hawley J. , Barrow J.R.
Published: April 2023

Purpose:

We aim to understand the impact of the COVID-19 on health care utilization and oral health conditions of patients at federally qualified health centers (FQHCs), where patients are disproportionately low income, publicly insured, or uninsured.

Methods:

Using deidentified electronic health records of patients at FQHCs in the United States from January 2019 through December 2020 ( n = 431,509), variations in health care utilization since the COVID-19 outbreak were observed by procedure types and patient characteristics. Changes in dental utilization and oral health conditions were characterized using mixed-effect negative binomial and logistic regression models.

Results:

Dental utilization decreased more drastically than medical utilization during shelter-in-place periods in 2020 and rebounded more slowly after the reopening. Greater demands for oral surgery and teledentistry and less demands for preventive services were observed in 2020. As compared to 2019, patients experienced more psychological stress–related dental conditions with odds ratios of 1.52 (95% confidence interval [CI], 1.31–1.76) for uninsured, 1.48 (95% CI, 1.07–2.02) for Medicaid enrollees, and 2.38 (95% CI, 1.68–3.40) for private insurance beneficiaries.

Conclusion:

As a result of COVID-19, patients received more invasive dental procedures due to delayed treatment and experienced a higher risk of psychological stress–related dental conditions. Continued support for statewide policies to expand access to oral health care and oral health promotion strategies for the vulnerable populations would be encouraged.

Knowledge Transfer Statement:

Our study describes the impact of COVID-19 on dental care use and oral health conditions at Federally Qualified Health Centers, targeted to provide care for some of the most vulnerable populations in the United States. The results of this retrospective cohort study can be used by clinicians and policymakers on understanding the clinical needs of the vulnerable populations after the pandemic. It highlights the need for continued support to expand access to oral health care and oral health promotion to these populations.
Interaction between cerebral small vessel disease, blood pressure, and remote ischemic lesions in acute spontaneous intracerebral hemorrhage
Authors: Chen Szu-Ju , Tsai Hsin-Hsi , Lo Yen-Ling , Chen Ya-Fang , Tang Sung-Chun , Jeng Jiann-Shing , Tsai Li-Kai
Published: April 2023

Background:

Acute blood pressure (BP) reduction is the first-line treatment for acute spontaneous intracerebral hemorrhage (ICH); however, recent research suggests that intensive BP reduction along with cerebral small vessel disease (cSVD) is a risk factor for remote DWI lesions (RDWILs). We aimed to delineate the interplay between cSVD and BP reduction therapy on the risk of RDWILs.

Methods:

We enrolled 303 patients who underwent brain magnetic resonance imaging within 7 days after acute spontaneous ICH. RDWILs were categorized as occurring in borderzone (BZ) or non-BZ areas. We examined the effect of cSVD, acute BP reduction, and their interaction on RDWILs.

Results:

RDWILs were observed in 34 (11%) patients (59.8 ± 10.3-years-old, 24% male). RDWILs were associated with a larger acute weighted average mean arterial pressure (MAP) reduction in the initial 24 h after ICH onset and a higher total cerebral microbleed (CMB) count. Intensive MAP changes (odds ratio (OR) per 10 mmHg 1.76, 95% confidence interval (CI) 1.03–3.20), total CMBs burden (OR per 10 CMBs 1.21, 95% CI 1.08–1.39), and presence of lobar CMBs (OR 7.33, 95% CI 1.59–55.6) were risk factors for RDWILs at BZ, but not at non-BZ. Furthermore, a significant interaction was observed between lobar CMBs and MAP reduction on increased risk of RDWILs at BZ ( p = 0.030).

Conclusion:

cSVD modulates the effect of acute BP reduction on the risk of RDWILs. Patients with extensive microangiopathy have a higher risk of developing cerebral ischemic changes in BZ during unstable hemodynamic status.
Report from the Third International Last Aid Conference: cultural diversity in palliative care
Authors: Zelko Erika , Bollig Georg
Published: April 2023

The Third International Last Aid Conference was held from October 28 to 29, 2022, as a hybrid event. Altogether, there were 85 participants from 14 different countries. The main topics of the conference were cultural diversity in palliative care, public palliative care education (PPCE), experience with Last Aid courses from different countries, and founding possibilities for courses and research in Last Aid. The speakers from different countries presented their experiences with Last Aid courses for adult and children, as well as the online courses. The contribution of the work of the Last Aid Research Group International (LARGI) for the development of Last Aid was presented. This report provides an overview of the conference and the content of presentations and highlights the most interesting discussions points.
The Role of Ultrasonography in Evaluating the Function of the Vocal Cords, Post-Thyroidectomy
Authors: Tosun Yasin , Çetin Kenan , Karatay Emrah , İnanç Ömer Faruk , Akçakoca Gizem
Published: April 2023

Objective:

Although there are several methods to assess vocal cord (VC) paralysis, direct flexible laryngoscopy (DFL) is used as a main diagnostic modality. In recent years, transcutaneous laryngeal ultrasonography (TLUS) has emerged as an alternative method to evaluate VCs. The objective of this study was to investigate the efficiency of TLUS in the evaluation of VCs, post-thyroidectomy.

Materials and Methods:

The study included 93 patients who had undergone thyroid surgery. All patients were examined using DFL, 1 to 3 days before surgery, to evaluate their VC functions. Patients were examined using DFL and TLUS on postoperative day 7. Patients’ age, sex, diagnosis, type of surgery, preoperative DFL findings, postoperative DFL, and TLUS findings were recorded.

Results:

Sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPVs) were 75% (6/8), 98.66% (74/75), 85.71% (6/7), and 97.36% (74/76), respectively. The diagnostic accuracy of TLUS was 97.96%. The area under the receiver operator characteristic (ROC) curve was 0.869, P value <.0001 (95% confidence inteval, 0.75–1.00), which indicated that TLUS was a good tool for identification of VC palsy in this cohort of post-thyroidectomy patients.

Conclusion:

This cohort study demonstrated that TLUS was a reliable diagnostic tool to evaluate VC functions in patients after thyroidectomy. It may be used as a safer alternative during the ongoing COVID-19 pandemic due to the lack of human-originated aerosols.
Genetic subdivisions of follicular lymphoma defined by distinct coding and noncoding mutation patterns
Authors: Dreval Kostiantyn , Hilton Laura K. , Cruz Manuela , Shaalan Haya , Ben-Neriah Susana , Boyle Merrill , Collinge Brett , Coyle Krysta M. , Duns Gerben , Farinha Pedro , Grande Bruno M. , Meissner Barbara , Pararajalingam Prasath , Rushton Christopher K. , Slack Graham W. , Wong Jasper , Mungall Andrew J. , Marra Marco A. , Connors Joseph M. , Steidl Christian , Scott David W. , Morin Ryan D.
Published: April 2023

Follicular lymphoma (FL) accounts for ∼20% of all new lymphoma cases. Increases in cytological grade are a feature of the clinical progression of this malignancy, and eventual histologic transformation (HT) to the aggressive diffuse large B-cell lymphoma (DLBCL) occurs in up to 15% of patients. Clinical or genetic features to predict the risk and timing of HT have not been described comprehensively. In this study, we analyzed whole-genome sequencing data from 423 patients to compare the protein coding and noncoding mutation landscapes of untransformed FL, transformed FL, and de novo DLBCL. This revealed 2 genetically distinct subgroups of FL, which we have named DLBCL-like (dFL) and constrained FL (cFL). Each subgroup has distinguishing mutational patterns, aberrant somatic hypermutation rates, and biological and clinical characteristics. We implemented a machine learning–derived classification approach to stratify patients with FL into cFL and dFL subgroups based on their genomic features. Using separate validation cohorts, we demonstrate that cFL status, whether assigned with this full classifier or a single-gene approximation, is associated with a reduced rate of HT. This implies distinct biological features of cFL that constrain its evolution, and we highlight the potential for this classification to predict HT from genetic features present at diagnosis.
Receptor-Like Cytoplasmic Kinase STK Confers Salt Tolerance in Rice
Authors: Zhou Yanbiao , Zhang Zhihui , Zhao Xinhui , Liu Lan , Tang Qianying , Fu Jun , Tang Xiaodan , Yang Runqiu , Lin Jianzhong , Liu Xuanming , Yang Yuanzhu
Published: April 2023

Background

Soil salinization is a major abiotic environmental stress factor threatening crop production throughout the world. Salt stress drastically affects the growth, development, and grain yield of rice (Oryza sativa L.), and the improvement of rice tolerance to salt stress is a desirable approach for meeting increasing food demand. Receptor-like cytoplasmic kinases (RLCKs) play essential roles in plant growth, development and responses to environmental stresses. However, little is known about their functions in salt stress. Previous reports have demonstrated that overexpression of an RLCK gene SALT TOLERANCE KINASE (STK) enhances salt tolerance in rice, and that STK may regulate the expression of GST (Glutathione S-transferase) genes.

Results

The expression of STK was rapidly induced by ABA. STK was highest expressed in the stem at the heading stage. STK was localized at the plasma membrane. Overexpression of STK in rice increased tolerance to salt stress and oxidative stress by increasing ROS scavenging ability and ABA sensitivity. In contrast, CRISPR/Cas9-mediated knockout of STK increased the sensitivity of rice to salt stress and oxidative stress. Transcriptome sequencing analysis suggested that STK increased the expression of GST genes (LOC_Os03g17480, LOC_Os10g38140 and LOC_Os10g38710) under salt stress. Reverse transcription quantitative PCR (RT-qPCR) suggested that four stress-related genes may be regulated by STK including OsABAR1, Os3BGlu6, OSBZ8 and OsSIK1.

Conclusions

These findings suggest that STK plays a positive regulatory role in salt stress tolerance by inducing antioxidant defense and associated with the ABA signaling pathway in rice.
In-vitro validated methods for encoding digital data in deoxyribonucleic acid (DNA)
Authors: Mortuza Golam Md , Guerrero Jorge , Llewellyn Shoshanna , Tobiason Michael D. , Dickinson George D. , Hughes William L. , Zadegan Reza , Andersen Tim
Published: April 2023

Deoxyribonucleic acid (DNA) is emerging as an alternative archival memory technology. Recent advancements in DNA synthesis and sequencing have both increased the capacity and decreased the cost of storing information in de novo synthesized DNA pools. In this survey, we review methods for translating digital data to and/or from DNA molecules. An emphasis is placed on methods which have been validated by storing and retrieving real-world data via in-vitro experiments.
Predicting disease genes based on multi-head attention fusion
Authors: Zhang Linlin , Lu Dianrong , Bi Xuehua , Zhao Kai , Yu Guanglei , Quan Na
Published: April 2023

Background

The identification of disease-related genes is of great significance for the diagnosis and treatment of human disease. Most studies have focused on developing efficient and accurate computational methods to predict disease-causing genes. Due to the sparsity and complexity of biomedical data, it is still a challenge to develop an effective multi-feature fusion model to identify disease genes.

Results

This paper proposes an approach to predict the pathogenic gene based on multi-head attention fusion (MHAGP). Firstly, the heterogeneous biological information networks of disease genes are constructed by integrating multiple biomedical knowledge databases. Secondly, two graph representation learning algorithms are used to capture the feature vectors of gene-disease pairs from the network, and the features are fused by introducing multi-head attention. Finally, multi-layer perceptron model is used to predict the gene-disease association.

Conclusions

The MHAGP model outperforms all of other methods in comparative experiments. Case studies also show that MHAGP is able to predict genes potentially associated with diseases. In the future, more biological entity association data, such as gene-drug, disease phenotype-gene ontology and so on, can be added to expand the information in heterogeneous biological networks and achieve more accurate predictions. In addition, MHAGP with strong expansibility can be used for potential tasks such as gene-drug association and drug-disease association prediction.
Signatures in in vitro infection of NSC-34 mouse neurons and their cell nucleus with Rickettsia helvetica
Authors: Kask Lena , Påhlson Carl , Staxäng Karin , Nilsson Kenneth
Published: April 2023

Background

Rickettsia helvetica, a spotted fever rickettsia, is transmitted to humans via ticks in Europe, North Africa, and Asia. The central nervous system is a crucial target for rickettsial diseases, which has been reported for 12 of the 31 species, of which R. helvetica is one. This study aimed, in an experimental model, to identify characteristics of R. helvetica infection in a mouse neuronal cell line, NSC-34.

Results

NSC-34, a fusion cell line of mouse motor spinal cord neurons and neuroblastoma cells, was used as a model. Propagation of R. helvetica in neurons was confirmed. Short actin tails were shown at the polar end of the bacteria, which makes it likely that they can move intracellularly, and even spread between cells. Another protein, Sca4, which with the cell adhesion protein vinculin enables the passage of the cell membrane, was expressed during infection. No significant increase in TNFα levels was seen in the infected neurons, which is of interest because TNFα protects the host cell from infection-induced apoptotic death which is crucial for host cell survival. The bacteria were also shown to invade and grow in the cell nucleus of the neuron.

Conclusions

The findings suggest that a R. helvetica infection may be harmful to NSC-34 neurons under these in vitro conditions, but the full effects of the infection on the cell need to be studied further, also on human neurons, to also understand the possible significance of this infection in relation to pathogenetic mechanisms.
Susceptibility antibiotic screening reveals high rates of multidrug resistance of Salmonella, Shigella and Campylobacter in HIV infected and uninfected patients from Mozambique
Authors: Hlashwayo Delfina F , Noormahomed Emília V , Bahule Leonilde , Benson Constance A , Schooley Robert T , Sigaúque Betuel , Barrett Kim E , Bila Custódio G
Published: April 2023

Background

Antibacterial resistance is a growing concern worldwide, including in Mozambique. Diarrhea is an important cause of mortality in Mozambique, yet few local studies have reported on the resistance of bacterial pathogens in this context. Therefore, this study aims to characterize antibiotic susceptibility patterns of Salmonella, Shigella and Campylobacter spp. among patients with diarrhea, including those who are HIV-infected and-uninfected.

Methods

We conducted antibiotic susceptibility testing on 157 stool isolates recovered from 129 patients aged between 0 and 80 years with diarrhea, including HIV infected (n = 68) and-uninfected individuals (n = 61), assisted at two health centers in Maputo city. The isolates comprised of 99 Salmonella, 45 Shigella and 13 Campylobacter strains. The Kirby-Bauer disk diffusion method was used on Mueller-Hinton II agar for Salmonella and Shigella spp., while Mueller-Hinton II agar with 5% defibrinated sheep blood was used for Campylobacter spp. We tested six antibiotics listed on the national essential medicines list, including ciprofloxacin, erythromycin, azithromycin, trimethoprim-sulfamethoxazole, gentamicin, and tetracycline.

Results

All isolates were resistant to at least one antibiotic. A high percentage of Salmonella spp. isolates were found to be resistant to trimethoprim-sulfamethoxazole (89.9%, n = 89), erythromycin (88.9%, n = 88) and tetracycline (76.8%, n = 76). In addition, 86.6% (n = 39) and 68.9% (n = 31) of Shigella isolates were resistant to trimethoprim-sulfamethoxazole and tetracycline, respectively. The majority of Campylobacter isolates (92.3%, n = 12) were resistant to erythromycin, azithromycin and tetracycline. Multidrug resistance (MDR) was observed in 79.8% of Salmonella spp., 76.9% of Campylobacter spp., and 57.8% of Shigella spp. Drug susceptibility profiles for Salmonella spp. and Campylobacter were similar in both HIV-1 infected and uninfected patients. However, Shigella spp. isolates obtained from patients without HIV infection were significantly more likely to be resistant to erythromycin, azithromycin or to exhibit multidrug resistance than those obtained from patients with HIV-1 infection (p < 0.05). All Shigella spp. and Campylobacter spp. isolates were susceptible to gentamicin.

Conclusion

Our study highlights concerning rates of antibiotic resistance and MDR among diarrheal bacterial pathogens in Mozambique. Further research is needed to understand the impact of HIV, ART therapy and immunosuppression on antibiotic resistance. Urgent interventions are essential to prevent the spread of resistant strains.
Protocol of a randomized controlled trial investigating Deep Brain Stimulation for MOtor symptoms in patients with Parkinson’s disease DEmentia (DBS-MODE)
Authors: Sisodia V. , Swinnen B. E. K. S. , Dijk J. M. , Verwijk E. , van Rooijen G. , Lemstra A. W. , Schuurman P. R. , de Bie R. M. A.
Published: April 2023

Background

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for disabling motor symptoms of Parkinson’s disease (PD) that persist despite optimal pharmacological treatment. Currently, DBS is not performed if there is concomitant significant cognitive impairment based on concerns of cognitive deterioration, higher complication rate and less functional improvement. However, this has not been investigated so far.

Methods

A single center, prospective, randomized, open-label, blinded end-point (PROBE design) pilot clinical trial is being performed. Patients are eligible for the trial if they have PD dementia (PDD), are able to provide informed consent, and experience disabling motor response fluctuations, bradykinesia, dyskinesia, or painful dystonia, despite optimal pharmacological treatment. In total 44 patients will be randomized to either STN-DBS accompanied by best medical treatment (DBS group) or to best medical treatment alone (BMT group). The primary outcome measure is the change from baseline to 30 weeks on the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale part III score in a standardized off-drug phase. The main secondary outcome measures consist of scales assessing cognitive aspects of daily living, neuropsychiatric symptoms and impulsive compulsive disorders. Additional secondary outcome measures include motor signs during on-drug phase, dyskinesia, motor fluctuations, cognitive performance, (severe) adverse events, treatment satisfaction, and caregiver burden. Patients will be followed during 52 weeks after randomization.

Discussion

The Deep Brain Stimulation for MOtor symptoms in patients with Parkinson’s disease DEmentia (DBS-MODE) trial directly compares the effectiveness and safety of DBS with BMT in patients with PDD.

Trial registration

The DBS-MODE trial has been registered in the International Clinical Trial Registry Platform (NL9361) on the 24thof March 2021 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9361).
Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer
Authors: Ao Yong-Qiang , Gao Jian , Zhang Ling-Xian , Deng Jie , Wang Shuai , Lin Miao , Wang Hai-Kun , Ding Jian-Yong , Jiang Jia-Hao
Published: April 2023

Background

The scavenger receptor CD36 was reported to be highly expressed on tumor-infiltrating CD8+ T cells, but the clinical role remains obscure. This study aims to explore the infiltration and clinical value of CD36+CD8+ T cells in NSCLC.

Methods

Immunohistochemistry and immunofluorescence were conducted for survival analyses and immunological evaluation in 232 NSCLC patients in Zhongshan Hospital. Flow cytometry analyses were carried out to assess the immune cells from fresh tumor samples, non-tumor tissues and peripheral blood. In vitro tumor infiltrating lymphocytes cultures were conducted to test the effect of CD36 blockage.

Results

Accumulation of CD36+CD8+ T cells in tumor tissues was correlated with more advanced stage (p < 0.001), larger tumor size (p < 0.01), and lymph node metastasis (p < 0.0001) in NSCLC. Moreover, high infiltration of CD36+CD8+ T cells indicated poor prognosis in terms of both overall survival (OS) and recurrence-free survival (RFS) and inferior chemotherapy response. CD36+CD8+ T cells showed decreased GZMB (p < 0.0001) and IFN-γ (p < 0.001) with elevated PD-1 (p < 0.0001) and TIGIT (p < 0.0001). Analysis of tumor-infiltrating immune cell landscape revealed a positive correlation between CD36+CD8+ T cells and Tregs (p < 0.01) and M2-polarized macrophages (p < 0.01) but a negative correlation with Th1 (p < 0.05). Notably, inhibition of CD36 partially restored the cytotoxic function of CD8+ T cells by producing more GZMB and IFN-γ.

Conclusion

CD36+CD8+ T cells exhibit impaired immune function and high infiltration of CD36+CD8+ T cells indicated poor prognosis and inferior chemotherapy response in NSCLC patients. CD36 could be a therapeutic target in combination with chemotherapy in NSCLC patients.