bluuebunny/crossref_metadata_2025 huggingface dataset:
Two novel mouse models of slow-wave-sleep enhancement in aging and Alzheimer’s disease
Authors: Ogbeide-Latario Oghomwen E , Ferrari Loris L , Gompf Heinrich S , Anaclet Christelle
Published: June 2022

Aging and Alzheimer’s disease (AD) are both associated with reduced quantity and quality of the deepest stage of sleep, called slow-wave-sleep (SWS). Slow-wave-sleep deficits have been shown to worsen AD symptoms and prevent healthy aging. However, the mechanism remains poorly understood due to the lack of animal models in which SWS can be specifically manipulated. Notably, a mouse model of SWS enhancement has been recently developed in adult mice. As a prelude to studies assessing the impact of SWS enhancement on aging and neurodegeneration, we first asked whether SWS can be enhanced in animal models of aging and AD.

The chemogenetic receptor hM3Dq was conditionally expressed in GABAergic neurons of the parafacial zone of aged mice and AD (APP/PS1) mouse model. Sleep–wake phenotypes were analyzed in baseline condition and following clozapine-N-oxide (CNO) and vehicle injections. Both aged and AD mice display deficits in sleep quality, characterized by decreased slow wave activity. Both aged and AD mice show SWS enhancement following CNO injection, characterized by a shorter SWS latency, increased SWS amount and consolidation, and enhanced slow wave activity, compared with vehicle injection. Importantly, the SWS enhancement phenotypes in aged and APP/PS1 model mice are comparable to those seen in adult and littermate wild-type mice, respectively. These mouse models will allow investigation of the role of SWS in aging and AD, using, for the first time, gain-of SWS experiments.
β-Arrestin 2 and Epac2 Cooperatively Mediate DRD1-Stimulated Proliferation of Human Neural Stem Cells and Growth of Human Cerebral Organoids
Authors: Dong Xiaoxu , Chen Yujie , Lu Juan , Huang Shichao , Pei Gang
Published: June 2022

G-protein-coupled receptors (GPCRs) reportedly relay specific signals, such as dopamine and serotonin, to regulate neurogenic processes although the underlying signaling pathways are not fully elucidated. Based on our previous work, which demonstrated dopamine receptor D1 (DRD1) effectively induces the proliferation of human neural stem cells, here we continued to show the knockout of β-arrestin 2 by CRISPR/Cas9 technology significantly weakened the DRD1-induced proliferation and neurosphere growth. Furthermore, inhibition of the downstream p38 MAPK by its specific inhibitors or small hairpin RNA mimicked the weakening effect of β-arrestin 2 knockout. In addition, blocking of Epac2, a PKA independent signal pathway, by its specific inhibitors or small hairpin RNA also significantly reduced DRD1-induced effects. Simultaneous inhibition of β-arrestin 2/p38 MAPK and Epac2 pathways nearly abolished the DRD1-stimulated neurogenesis, indicating the cooperative contribution of both pathways. Consistently, the expansion and folding of human cerebral organoids as stimulated by DRD1 were also mediated cooperatively by both β-arrestin 2/p38 MAPK and Epac2 pathways. Taken together, our results reveal that GPCRs apply at least 2 different signal pathways to regulate neurogenic processes in a delicate and balanced manners.
Assessing a pilot co-operative-based workshop-subsidy model toward improving small-scale chicken production in peri-urban Nepal
Authors: Acosta Sarai , Chen Ruby , Nhemaphuki Sunita , Khanal Damber , Cadena Myrna , Pitesky Maurice , Erbstein Nancy , Niemeier Deb
Published: June 2022

Farmers in Nepal face many of the same global challenges associated with initiating and scaling poultry husbandry as many other developing countries. These include access to innovative approaches in finance, credit, coop design, marketing, and sales. As with most low-income countries, Nepalese poultry farmers also lack adequate training in poultry husbandry including biosecurity. In this paper, we describe a collaborative workshop-subsidy approach to addressing these challenges conducted by a partnership with the UC Davis School of Veterinary Medicine, the College of Engineering, the School of Education, and a farming co-operative based in the semi-rural area of Bhaktapur, Nepal. The program included two workshops covering aspects of poultry rearing including coop construction, chick rearing, biosecurity, and husbandry. Both workshops were a combination of lectures and hands-on learning. Following completion of the workshops, each farmer received subsidized materials for coop construction and poultry rearing. The co-operative provided training facilities and a market for selling eggs. Despite an outbreak of Highly Pathogenic Avian Influenza (HPAI), which affected the scale of program implementation, our results suggest that the workshop subsidy collaborative approach can be successful in reducing market entry barriers. Our 6-mo post-workshop survey showed that two-thirds of the workshop participants ultimately built their own coop and raised chicks. Half of these participants reported market available egg production and a doubling of egg consumption at home.
The characterization of multiple novel paramyxoviruses highlights the diverse nature of the subfamilyOrthoparamyxovirinae
Authors: Vanmechelen Bert , Meurs Sien , Horemans Marie , Loosen Arne , Joly Maes Tibe , Laenen Lies , Vergote Valentijn , Koundouno Fara Raymond , Magassouba N’Faly , Konde Mandy Kader , Condé Ibrahima Sory , Carroll Miles W , Maes Piet
Published: June 2022

The subfamily Orthoparamyxovirinae is a group of single-stranded, negative-sense RNA viruses that contains many human, animal, and zoonotic pathogens. While there are currently only forty-two recognized species in this subfamily, recent research has revealed that much of its diversity remains to be characterized. Using a newly developed nested PCR-based screening assay, we report here the discovery of fifteen orthoparamyxoviruses in rodents and shrews from Belgium and Guinea, thirteen of which are believed to represent new species. Using a combination of nanopore and sanger sequencing, complete genomes could be determined for almost all these viruses, enabling a detailed evaluation of their genome characteristics. While most viruses are thought to belong to the rapidly expanding genus Jeilongvirus, we also identify novel members of the genera Narmovirus, Henipavirus, and Morbillivirus. Together with other recently discovered orthoparamyxoviruses, both henipaviruses and the morbillivirus discovered here appear to form distinct rodent-/shrew-borne clades within their respective genera, clustering separately from all currently classified viruses. In the case of the henipaviruses, a comparison of the different members of this clade revealed the presence of a secondary conserved open reading frame, encoding for a transmembrane protein, within the F gene, the biological relevance of which remains to be established. While the characteristics of the viruses described here shed further light on the complex evolutionary origin of paramyxoviruses, they also illustrate that the diversity of this group of viruses in terms of genome organization appears to be much larger than previously assumed.
Begomovirus Tomato Leaf Curl New Delhi Virus Is Seedborne but Not Seed Transmitted in Melon
Authors: Fortes Isabel M. , Pérez-Padilla Verónica , Romero-Rodríguez Beatriz , Fernández-Muñoz Rafael , Moyano Cristina , Castillo Araceli G. , De León Leandro , Moriones Enrique
Published: June 2022

Seed transmission can be of considerable relevance to the dissemination of plant viruses in nature and for their prevalence and perpetuation. Long-distance spread of isolates of the begomovirus species Tomato leaf curl New Delhi virus (genus Begomovirus, family Geminiviridae) has recently occurred from Asia to the Middle East and the Mediterranean Basin. Here, we investigated the possible transmission by melon (Cucumis melo L.) seeds of a tomato leaf curl New Delhi virus (ToLCNDV) isolate of the “Spain” strain widely distributed in the Mediterranean area as an alternative mechanism for long-distance spread. PCR amplification detection of ToLCNDV in floral parts and mature seeds of melon plants reveals that this virus is seedborne. “Seedborne” is defined as the ability of a virus to be carried through seeds, which does not necessarily lead to transmission to the next generation. Treatment with a chemical disinfectant significantly reduced the detectable virus associated with melon seeds, suggesting ToLCNDV contamination of the external portion of the seed coat. Also, when the internal fraction of the mature seed (seed cotyledons + embryo) was analyzed by quantitative PCR amplification, ToLCNDV was detectable at low levels, suggesting the potential for viral contamination or infection of the internal portions of seed. However, grow-out studies conducted with melon progeny plants germinated from mature seeds collected from ToLCNDV-infected plants and evaluated at early (1-leaf) or at late (20-leaf) growth stages did not support the transmission of ToLCNDV from seeds to offspring.
First Report of the Satellite DNA Beta Associated with Tomato Yellow Leaf Curl Virus – Mild on Tomato in Iraq
Authors: Abass M. O. , Lahuf A. A.
Published: June 2022

In November 2021, severe symptoms of TYLCV disease were observed in tomato fields in Karbala Province, Iraq. Symptomatic tomato samples were observed on 20 to 30% of plants. Samples of symptomatic plants were collected randomly. TYLCV-specific PCR primers were employed to confirm the presence of the virus. Total DNA was extracted and used as templates for next-generation sequencing. The unmapped reads were subjected to de novo assembly. The contigs assembled were compared with GenBank data of plant viruses. A BLASTn analysis revealed 99.34% similarity with tomato yellow leaf curl virus-mild (MT583814.1). This finding was confirmed by a PCR test using specific primers. Additionally, there was 94.66% pairwise identity with cotton leaf curl Gezira betasatellite (CLCuGB) isolate Al-Ain (KM279620.1). The universal primer pair for detection of betasatellites was applied, followed by Sanger sequencing of the amplicons, which confirmed the infection of all the tested plants with CLCuGB. The DNA sequence of CLCuGB has accession number ON206651. To verify the presence of TYLCV-mild and betasatellite, a field survey was conducted in the main regions of tomato cultivation in Karbala Province, Iraq, in November 2021. Symptomatic leaf samples were collected randomly from 40 fields and analyzed for virus infections. This analysis revealed that the virus and its satellite are distributed throughout the province. To our knowledge, this is the first record of occurrence and complete genome sequence of CLCuGB, associated with TYLCV-mild, in tomato fields in Iraq.
Use of Outcome Measures by Certified Lymphedema Therapists With Survivors of Breast Cancer With Breast Cancer–Related Lymphedema
Authors: Doubblestein David Aaron , Spinelli Bryan A. , Goldberg Allon , Larson Cathy A. , Yorke Amy M.
Published: June 2022

Background:

Survivors of breast cancer (SBC) with breast cancer–related lymphedema (BCRL) have demonstrated neuromusculoskeletal restrictions, sensorimotor impairments, postural instability, and balance deficits. To date, there have been no studies that investigate outcome measures (OMs) used by certified lymphedema therapists (CLTs) with SBC with BCRL.

Objective:

The purposes of this study were to (1) determine types of OMs used and their frequency of use by CLTs with SBC with BCRL and their differences between therapy professions, and (2) identify unique characteristic predictors for use of OMs.

Methods:

Cross-sectional online survey research design. Electronic surveys were distributed to CLTs from various institutions. Data from 70 physical therapists (PTs) and 41 occupational therapists were analyzed from 130 completed surveys.

Results:

Sixteen OMs used most often assessed joint function, flexibility, strength, pain, volume, sensation, tissue consistency, body composition, health-related quality of life, and upper quadrant function. There were differences between PTs and occupational therapists in use of OMs. Lymphology Association of North America certification, practice setting, and profession (physical therapy and occupational therapy) predicted the use of some OMs.

Conclusions:

This study identified individual OMs used on SBC with BCRL in clinical practice among interdisciplinary CLTs. The number of OMs used to assess body functions and structures exceed those OMs for activities and participation, which may be influenced by CLT profession, Lymphology Association of North America certification, and level of highest degree.
Does Hip Fracture Admitting Service Affect Proper Deep Venous Thrombosis Prophylaxis? An Investigation at a Level 1 Trauma Center
Authors: Diedring Ben , Knapp Paul , Bandovic Ivan , Druskovich Katherine , Waldron Jacob , Denisiuk Marek , Frisch Nicholas , Afsari Alan , Hayward Richard , Best Benjamin
Published: June 2022

Objective:

To examine if rates of appropriate thromboprophylaxis prescribing at the time of discharge would be higher in patients admitted to the orthopaedic service. Second, to see if improvements could be made in the rates of these missed events after a structured intervention.

Design:

Retrospective Cohort Study, Prospective Interventional.

Setting:

Level 1 Academic Hospital.

Patients:

Two hundred forty-six patients undergoing a hip hemiarthroplasty for femoral neck fracture discharged to an extended care facility.

Intervention:

A letter was sent to the internal quality control committee detailing our preintervention study.

Main Outcome Measure:

We looked at the differences among admitting services for missed thromboembolic prophylaxis (TPx) at the time of hospital discharge and rates of appropriate TPx after a structured intervention.

Results:

No statistically significant differences existed in relation to patient age, gender, body mass index, or postoperative discharge day in the preintervention group. Orthopaedic surgery prescribed adequate TPx at discharge for 76 of 77 patients (98.7%), general trauma surgery for 26 of 30 patients (86.7%), and internal medicine for 85 of 96 patients (86.7%) in the preintervention group. There was a statistically significant difference when comparing adequate TPx between orthopaedic surgery and other services (P < 0.013 and <0.021, respectively). Our postintervention data found a significant decrease in the rates of missed TPx on discharge. In our preintervention sample group compared with our postintervention sample group, we saw a decrease in missed TPx of 5/39 versus 0/43 events (P = 0.021).

Conclusions:

We found that a letter sent to all members of a hospital internal quality committee decreased incidences of missed TPx. Specifically, this letter explained the details of our study that kept track of rates of missed TPx among different admitting services. We found that after our intervention, which consisted of a letter and a multidisciplinary discussion, the rate of missed thromboembolic prophylaxis events improved from 5/39 (12%) to 0/43 (0%) (P = 0.021).

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Exploring Virtual Teaching Approaches Among Pediatricians During the SARS-CoV-2 Pandemic: A Virtual Ethnographic Study
Authors: Rashid Marghalara , Nguyen Julie , Foulds Jessica L. , Forgie Sarah E.
Published: June 2022

Introduction:

During the SARS-CoV-2 pandemic, Canadian postsecondary institutions were forced to rely on online teaching to comply with physical distancing recommendations. This sole reliance on virtual methods to deliver synchronous teaching sessions in medical education was novel. We found little empirical research examining pediatric educators' experiences. Hence, the objective of our study was to describe and gain a deeper understanding of pediatric educators' perspectives, focusing on the research question, “How is synchronous virtual teaching impacting and transforming teaching experiences of pediatricians during a pandemic?”

Methods:

A virtual ethnography was conducted guided by an online collaborative learning theory. This approach used both interviews and online field observations to obtain objective descriptions and subjective understandings of the participants' experiences while teaching virtually. Pediatric educators (clinical and academic faculty) from our institution were recruited using purposeful sampling and invited to participate in individual phone interviews and online teaching observations. Data were recorded and transcribed, and a thematic analysis was conducted.

Results:

Fifteen frontline pediatric teachers from our large Canadian research-intensive university were recruited. Four main themes, with subthemes, emerged: (1) the love/hate relationship with the virtual shift; (2) self-imposed pressure to increase virtual engagement; (3) looking back, moving forward; (4) accelerated adaptation and enhanced collaboration.

Conclusion:

Pediatricians adopted new delivery methods quickly and found many efficiencies and opportunities in this shift. Continued use of virtual teaching will lead to increased collaboration, enhanced student engagement strategies, and blending the advantages of virtual and face-to-face learning.
CD8+ T-cell responses in HIV controllers: potential implications for novel HIV remission strategies
Authors: Rutishauser Rachel L. , Trautmann Lydie
Published: June 2022

Purpose of review

Immunological studies of spontaneous HIV and simian virus (SIV) controllers have identified virus-specific CD8+ T cells as a key immune mechanism of viral control. The purpose of this review is to consider how knowledge about the mechanisms that are associated with CD8+ T cell control of HIV/SIV in natural infection can be harnessed in HIV remission strategies.

Recent findings

We discuss characteristics of CD8+ T-cell responses that may be critical for suppressing HIV replication in spontaneous controllers comprising HIV antigen recognition including specific human leukocyte antigen types, broadly cross-reactive T cell receptors and epitope targeting, enhanced expansion and antiviral functions, and localization of virus-specific T cells near sites of reservoir persistence. We also discuss the need to better understand the timing of CD8+ T-cell responses associated with viral control of HIV/SIV during acute infection and after treatment interruption as well as the mechanisms by which HIV/SIV-specific CD8+ T cells coordinate with other immune responses to achieve control.

We propose implications as to how this knowledge from natural infection can be applied in the design and evaluation of CD8+ T-cell-based remission strategies and offer questions to consider as these strategies target distinct CD8+ T-cell-dependent mechanisms of viral control.
Study of Low-Dose Radiation Workers Ionizing Radiation Sensitivity Index and Radiation Dose-Effect Relationship
Authors: Liu Gang , Zhang Rong , Li Ye , Wu Xiao Qin , Niu Li Mei , Liu Yin Yin , Zhang Xue
Published: June 2022

Background

In the present study, we analyzed radiation injuries to Chinese workers exposed to low-dose radiation. We discuss the relationships between dose and injury.

Methods

This study randomly selected 976 radiation workers who underwent occupational health monitoring. The radiation workers were divided into 5 different types of work: radiation diagnosis, radiation therapy, interventional therapy, nuclear medicine, and industrial inspection. This research was approved by the Bioethics Committee at the Gansu Provincial Center for Disease Control and Prevention.

Results

The average annual cumulative dose to interventional radiation workers was the highest, i.e., 0.86 mSv. The detection rate of lens opacity was 37%, but 99.70% of lens opacities occurred in the peripheral cortex. Posterior subcapsular opacification was detected less than 1.00% of the time. The rate of chromosomal aberrations was highest for radiological workers with more than 20 years of service. Annual cumulative dose reached 2.04 mSv, and the monitoring dose for 3 months was as high as 1.62 mSv. Dicentric chromosomes were also detected. The manual packaging and drug delivery nuclear medicine staffs totaled 14 individuals. 131131 was detected in the thyroids of 4 workers (28.57%). The detection rate of thyroid 131I was higher in the hand-packed and administered group than in the automatic administration group.

Conclusion

Radiation workers exposed to low doses of radiation can sustain injuries. Interventional radiology workers receive the highest doses and sustain the most significant effects. This study suggests that chromosome aberration analysis is an important index in occupational health monitoring of radiological workers. Monitoring of internal radiation exposure cannot be ignored for nuclear medicine staff.
Specific Absorbed Fractions for Spontaneous Fission Neutron Emitters in the ICRP Reference Pediatric Voxel Phantom Series
Authors: Griffin Keith T. , Eckerman Keith F. , Manger Ryan P. , Jokisch Derek W. , Bolch Wesley E. , Hertel Nolan E.
Published: June 2022

Specific absorbed fractions (SAFs) are key components in the workflow of internal exposure assessment following the intake of a radionuclide, allowing quick conversion of particle energy released in a source region to the expected absorbed dose in target regions throughout the body. For data completeness, SAFs for spontaneous fission neutron emitters are currently needed for the recently adopted ICRP reference pediatric voxel phantom series. With 77 source regions within each reference individual and 28 radionuclides decaying via spontaneous fission, full Monte Carlo simulation requires significant computation time. In order to reduce this burden, a novel method for neutron SAF estimation was undertaken. The Monte Carlo N-Particle version 6.1 (MCNP6) simulation package was chosen to simulate the 252Cf Watt fission neutron spectrum originating from 15 source regions in each phantom; dose estimation within 41 target tissues allowed for assessment of the SAF value for each source-target pair. For the remaining source regions, chord length distributions were computed using MATLAB code to determine the separation between the source-target pairs within the pediatric phantom series. These distance distributions were used in conjunction with a 252Cf neutron dose point kernel calculated in soft tissue, which was modified to account for the source region’s depth from the surface of the body. Lastly, the 252Cf SAF dataset was extended to the other 27 spontaneous fission neutron emitters based on differences in the Watt fission spectrum parameters of each radionuclide. This methodology has been shown to accurately estimate spontaneous fission neutron SAFs to within 20% of the Monte Carlo estimated value for most source-target pairs in the ICRP reference pediatric series.
Pilot Study of Thoron Concentration in an Underground Thorium Mine
Authors: Lindsay R. , Mngonyama S. , Molahlehi P. , Ngwadla X. E. , Ramonnye G. J.
Published: June 2022

The Steenkampskraal mine in the Western Cape Province in South Africa provides some interesting challenges for radiation protection practitioners in view of the high thoron values encountered in this mine. The mine contains high natural thorium concentrations that lead to high thoron activity concentrations, as will be shown in this paper. The influence of ventilation has been studied, and the source term has been investigated by considering the thorium content of the rocks and the thoron exhalation. The thoron activity concentrations are around 10 kBq m−3 at a monazite seam, and the thorium exhalation is consistent with these levels. The thoron concentrations can be reduced by ventilation but not eliminated. However, the thoron progeny can probably be reduced dramatically. Issues that affect the thoron levels are also discussed. Further studies are needed, but the thoron may well not be a radiation protection problem despite the high thoron concentrations.
Effect of Omega-3 on HLA-DR Expression by Conjunctival Cells and Tear Cytokine Concentrations in the Dry Eye Assessment and Management Study
Authors: Roy Neeta S. , Yu Yinxi , Ying Gui-Shuang , Maguire Maureen G. , Asbell Penny A. ,   for the DREAM Study Group
Published: June 2022

Objectives:

To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, interferon-γ, and tumor necrosis factor-α in dry eye disease patients in the Dry Eye Assessment and Management study.

Methods:

Patients were randomized to receive a daily dose of eicosapentaenoic and docosahexaenoic acids (ω3) or refined olive oil (placebo) for 12 months. At baseline, 6 and 12 months, HLA-DR expression in conjunctival total, epithelial, and white blood cells and cytokine concentration in tears were determined. Differences in change from baseline between treatment groups were assessed using generalized estimating equations (HLA-DR) or Wilcoxon rank–sum test (cytokines).

Results:

No differences were observed in HLA-DR expression in total, epithelial, or white blood cells between ω3 and placebo groups at 6 months (n=435) or 12 months (n=436). The median concentration percent change differed between ω3 and placebo groups at 6 months for IL-6 (−36.6 vs. 24.5%, P=0.02, n=75) and for IL-8 (3.7% vs. 72.6%, P=0.02, n=68); at 12 months, they did not differ (P≥0.18). No other differences between the treatment groups were detected.

Conclusions:

ω3 supplementation did not consistently affect ocular inflammatory status as measured by the frequency of HLA-DR expressing conjunctival cells or tear cytokines.
Coexistence of submandibular epithelioid angiosarcoma and papillary thyroid carcinoma: A case report
Authors: Liu Yi-Ting , Wang Jing , Sui Yan-Xia , Zhao Dong-Li
Published: June 2022

Introduction:

Reports on the coexistence of epithelioid angiosarcoma (EA) and papillary thyroid carcinoma (PTC) are rare. Over the past 50 years, only 2 cases of coexistence of EA and PTC have been reported in English literature. Therefore, we report a rare case of coexistence of EA and PTC treated with surgery and adjuvant radiation therapy.

Patient concerns:

A 64-year-old man visited our hospital with a painless mass in the left submandibular gland, with poor mobility.

Diagnosis:

Neck ultrasonography revealed nodules in the left submandibular gland and multiple cystic-solid mixed nodules in the left thyroid gland. Pathological findings revealed coexistence of EA in the left submandibular gland area and PTC in the left thyroid gland.

Interventions:

The patient underwent resection of the left submandibular gland, deep maxillofacial tumor, total thyroidectomy, left neck I, II, III, and VI regional lymph node dissection, and recurrent laryngeal nerve exploration under general anesthesia. Two months postoperatively, the patient also received adjuvant radiation therapy in the local and adjacent areas, with 4MV-X IMRT DT50GY at 2Gy/day 25 fractions.

Outcomes:

The follow-up period was 37 months. The patient recovered well without focal neurological deficits, local recurrence, or distant metastasis after surgery, except for grade I skin reaction after adjuvant radiation therapy.

Conclusions:

This is a rare case report of the coexistence of EA in the left submandibular gland and PTC in the left thyroid gland. Although multiple examinations were used, precise preoperative diagnosis was challenging owing to the coexistence of EA and PTC. Surgery and radiotherapy were effective treatments for the coexistence of EA and PTC in this case.
Role of tyrosine kinase inhibitor in chronic myeloid leukemia patients with SARS-CoV-2 infection: A narrative Review
Authors: Asif Muhammad , Amir Muhammad , Hussain Abrar , Achakzai Niaz M. , Natesan Pushparaj Peter , Rasool Mahmood
Published: June 2022

Severe acute respiratory syndrome (SARS) caused by a novel coronavirus-2 (CoV-2), also known as COVID-19, has spread rapidly worldwide since it is recognized as a public health emergency and has now been declared a pandemic on March 11, 2020, by the World Health Organization.

The genome of SARS-CoV-2 comprises a single-stranded positive-sense RNA approximately 27 to 30 kb in size. The virus is transmitted through droplets from humans to humans. Infection with the SARS virus varies from asymptomatic to lethal, such as fever, cough, sore throat, and headache, but in severe cases, pneumonia and acute respiratory distress syndrome.

Recently, no specific and effective treatment has been recommended for patients infected with the SARS virus. However, several options can be investigated to control SARS-CoV-2 infection, including monoclonal antibodies, interferons, therapeutic vaccines, and molecular-based targeted drugs.

In the current review, we focus on tyrosine kinase inhibitor management and their protective role in SARS-CoV-2 patients with chronic myelogenous leukemia.
Temporal trend of mortality and hospitalization for chronic kidney disease in adults from Northern Brazil
Authors: Rodrigues Alliny Sales , de Abreu Luiz Carlos , Morais Mauro Jose de Deus , Leitao Francisco Naildo Cardoso , do Amaral Gardenia Lima Gurgel , de Sousa Santos Edige Felipe , do Souto Ricardo Peres
Published: June 2022

We aimed to evaluate mortality and hospital admissions for chronic kidney disease in young adults according to sex and state in the northern region of Brazil, between 1996 and 2017. A population-based time series study using official data on mortality and hospital admissions due to chronic kidney disease in individuals aged 20 to 49 years old, residents of the northern region of Brazil, in the periods 1996–2017 and to 2008–2017, respectively. Chronic kidney disease was defined according to the International Classification of Diseases, 10th revision (N18).

The evolution of mortality from chronic kidney disease decreased by 0.881% per year over the period (1996–2017). In the states of Acre and Amapá, there was a reduction of 5.85% and –5.68% per year, respectively, and in Tocantins, an increase of 4.16% per year. The incidence of hospitalization did not vary between 2008 and 2017. However, 2 states showed an increase in hospitalization rates: Acre (6.08% per year) and Pará (2.83% per year), and 2 states showed a reduction: Amazonas (5.09% per year) and Tocantins (6.23% per year).

In general, there was decrease in mortality rate overtime. However, rate of mortality due to chronic kidney disease increased in the state of Tocantins. The evolution of hospitalization due to chronic kidney disease in a population of young adults remained stationary.
Epidural administration of 2% Mepivacaine after spinal anesthesia does not prevent intraoperative nausea and vomiting during cesarean section: A prospective, double-blinded, randomized controlled trial
Authors: Kita Takayuki , Furutani Kenta , Baba Hiroshi
Published: June 2022

Background:

Intraoperative nausea and vomiting (IONV) is a common symptom during cesarean section (CS) delivery causing significant discomfort to patients. Combined spinal and epidural anesthesia (CSEA) can provide both intraoperative anesthesia and postoperative analgesia. During CSEA, it is reasonable to administer local anesthetics to the epidural space before patient complaints to compensate for the diminished effect of spinal anesthesia. Therefore, we hypothesized that intraoperative epidural administration of 2% mepivacaine would reduce the incidence of IONV.

Methods:

Patients who were scheduled for elective CS were randomly allocated to 2 groups. Patients and all clinical staff except for an attending anesthesiologist were blinded to the allocation. After the epidural catheter was inserted at the T11–12 or T12–L1 interspace, spinal anesthesia was performed at the L2–3 or L3–4 interspace to intrathecally administer 10 mg of 0.5% hyperbaric bupivacaine. Twenty min after spinal anesthesia, either 5 mL of 2% mepivacaine (group M) or saline (group S) was administered through an epidural catheter. Vasopressors were administered prophylactically to keep both the systolic blood pressure ≥ 80 % of the baseline value with the absolute value ≥ 90 mm Hg and the mean blood pressure ≥ 60 mm Hg. The primary endpoint was the incidence of IONV. The secondary endpoints were degree of nausea, the degree and incidence of pain, and Bromage score.

Results:

Ninety patients were randomized, and 3 patients were excluded from the final analysis. There was no significant difference in the incidence of IONV between the groups (58% in group M and 61% in group S, respectively, P = .82). In contrast, the incidence and degree of intraoperative pain in group M were significantly lower compared to group S. In addition, the incidence of rescue epidural administration of fentanyl (18% vs 47%) or mepivacaine (2.3% vs 25%) for intraoperative pain was lower in group M compared to group S.

Conclusions:

Our results indicate that epidural administration of 2% mepivacaine 20 minutes after spinal anesthesia does not reduce the incidence of IONV in CS under CSEA. However, intraoperative epidural administration of 2% mepivacaine was found to improve intraoperative pain.
To study the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer based on network pharmacology
Authors: Wang Zijuan , Meng Lingpeng , Shan Jingyi , Pei Liangyu , Bao Leri , Li Xi , Lin Yudong , Gu Xian , Xu Zhenye
Published: June 2022

The aim of the study wasto explore the target and potential mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer infection by network pharmacology.

The target information of baicalein and flavonin was mined from CTD database and Swiss database. Genecards database, DRUGBANK database, and OMIM database were used to search for lung cancer related genes. The target protein network map (PPI) was drawn by using the STRING database analysis and Cytoscape3.7.1 software. With the help of Perl language, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were carried out by using the biological program package of R language.

In total, 347 biological targets of Astragaloside and Scutellariae Radix were identified through the collection and analysis of multiple databases. In total, 1526 lung cancer targets were obtained from a multi-disease database. The “component-target” network of Astragaloside and Scutellariae Radix was constructed, and the protein interaction network (PPI) of the overlapping targets was analyzed to identify the key targets of drug-influenced diseases. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer.

Scutellariae Radix and Astragaloside have the characteristics of multi-component, multi-target and multi-pathway in the treatment of lung cancer, which provides a new idea and scientific basis for further research on the molecular mechanism of the antilung cancer effect of Scutellariae Radix and Astragaloside.
Surgical treatment of interstitial pregnancy without cornual resection: A case report
Authors: Feng Qian , Zhong Jie , Liu Yujie , Li Shu-Ting , Zong Lili
Published: June 2022

Rationale:

Interstitial pregnancy (IP) is a rare but extremely life-threatening form of ectopic pregnancy. The traditional surgical treatment for this anomaly is the resection of uterine cornua or fallopian tubes, which often damages their structural integrity, thereby compromising the reproductive potential for women who wish to preserve fertility.

Patient concerns:

A 33-year-old female was admitted to our hospital with suspected ectopic pregnancy, following a 4-weeks history of positive pregnancy tests after uterine evacuation. The patient was hemodynamically stable on arrival. Ultrasound revealed an empty uterus with an eccentric gestational sac located at the fundus and surrounded by a thin myometrium, indicative of a suspected interstitial pregnancy.

Diagnosis and intervention:

After failed attempt at medical management with a single dose of intramuscular methotrexate, the patient was arranged for hysteroscopy-assisted laparoscopy. In surgery, the uterine cavity appeared empty, and a 2 × 2 cm bulge with increased vascularity at the right uterine courna was identified upon examination. The gestational sac was aspirated through the vagina from the right ostium of the uterine tube using a suction curette pointing at the right ostium. Sutures were not needed afterward, and the myometrial anatomy was left undisrupted. The diagnosis of IP was confirmed by the postoperative histological report.

Outcomes:

Perioperative blood loss was approximately 10 ml and the operative time was 40 minutes. The patient had an uneventful postoperative recovery and was discharged after 3 days. Subsequent follow-ups showed a significant reduction in the patient serum beta hCG to 48IU/L within 5 days postoperation, and a negative result after 7 days.

Lessons:

This novel surgical technique is an alternative minimally-invasive approach for selected early diagnosed and hemodynamically stable IP patients. The technique represents a safe, quick, and simple approach combining the benefits of laparoscopy, such as allowing for immediate conversion of cornuectomy when uterus ruptures, and the benefits of suction curettage, such as shorter operative time and minimal blood loss. We believe patients with interstitial pregnancy who still have fertility wishes would benefit from this surgical technique to a larger extent in the future.
Severe and refractory hypocalcaemia secondary to osteoblastic bone metastases in bladder signet ring carcinoma: A case report and literature review
Authors: Zeng Wanling , Swee Du Soon
Published: June 2022

Rationale:

Symptomatic hypocalcaemia is uncommon, occurring in <2% of patients with malignancy. Osteoblastic bone metastasis as a cause of hypocalcaemia is rare and not reported in bladder cancer.

Patient concerns:

We report a case of refractory hypocalcaemia in a patient with bladder cancer with extensive osteoblastic bone metastases. A 64-year-old male with a history of signet ring bladder carcinoma with osteoblastic bone metastases presented with severe hypocalcaemia with corrected calcium of 1.64 (2.09–2.46) mmol/L as well as hypomagnesemia and hypophosphatemia. He was previously treated with chemotherapy and immunotherapy. Denosumab was also initiated for the prevention of skeletal-related events.

Diagnoses:

Additional investigations showed significantly elevated bone formation markers N-terminal propeptide of type I procollagen and alkaline phosphatase. Chest radiography and computed tomography scan also demonstrated extensive areas of sclerotic bone lesions suggestive of osteoblastic bone metastases. He was diagnosed with severe hypocalcaemia secondary to osteoblastic bone metastases and partly to denosumab, vitamin D deficiency, and hypomagnesemia.

Interventions:

He was treated aggressively with calcium and vitamin D replacement.

Outcomes:

Despite prolonged intravenous calcium replacement and high doses of oral calcium, cholecalciferol, and calcitriol replacement, he had persistent hypocalcaemia with calcium levels ranging from 1.8 to 1.9 mmol/L. He died 4 months after his admission.

Lessons:

Osteoblastic bone metastases lead to an increased influx of calcium and phosphate into the bone leading to hypocalcaemia and should be considered as a differential in severe and refractory hypocalcaemia. It is rare and has not been described in bladder cancer. Precaution should be taken upon the initiation of antiresorptive in patients with osteoblastic bone metastases.
Risk factors for in-hospital death in elderly patients over 65 years of age with dementia: A retrospective cross-sectional study
Authors: Meng Zhangmin , Cheng Linan , Hu Xiuying , Chen Qian
Published: June 2022

As the population continues to age, dementia is becoming a huge social, economic, and healthcare burden. However, the risk factors for in-hospital death in elderly patients over 65 years of age with dementia are not well understood. Identifying factors that affect their prognosis could help clinicians with scientific decision-making.

To examine the risk factors for in-hospital death in elderly patients over 65 years of age with dementia in the Geriatric Department of West China Hospital.

In this retrospective, cross-sectional study, we analyzed inpatients aged ≥65 years with dementia between 2010 and 2016 using electronic medical records from the Information Center of West China Hospital. The risk factors for death were assessed using multivariable logistic regression.

Out of a total of 2986 inpatients with dementia, 3.4% died. Patient deaths were related to digestive diseases, respiratory diseases, circulatory diseases, urinary diseases, and chronic obstructive pulmonary disease, whereas patient survival was associated with osteoporosis and Parkinson disease. Patients with a mean length of hospital stay of ≥60 days had an increased risk of death (all P <.05). In the multiple logistic regression analysis, age ≥80 years, digestive diseases, respiratory diseases, urinary diseases, diabetes, chronic obstructive pulmonary disease, and ≥7 comorbidities were risk factors for death.

Mortality in hospitalized older patients with dementia is low, but some risk factors may be easily ignored. These findings could raise awareness among clinicians and caregivers about risk factors in hospitalized older patients, particularly hospitalized elderly patients with multiple comorbidities. Therefore, to reduce mortality, early prevention and management of potential risks are necessary.
Prevalence and correlates of COVID-19 vaccine hesitancy among the elderly in Qatar: A cross-sectional study
Authors: Abdul Karim Mustafa , Reagu Shuja M. , Ouanes Sami , Waheed Khan Abdul , Smidi Wesam S. , Al-Baz Nadeen , Alabdulla Majid
Published: June 2022

Older individuals are more vulnerable to severe coronavirus disease 2019 and medical complications. Vaccination stands as an efficient and safe vanguard against infection. However, negative attitudes and perceptions pertaining to available vaccines might hinder community inoculation. The aim of this study was to assess vaccine hesitancy and its psychosocial determinants among the elderly in Qatar.

We conducted a cross-sectional study between October 15 and November 15, 2020, using a composite online survey including the Vaccine Attitudes Examination Scale in addition to questions on sociodemographic correlates and the role of healthcare professionals.

The vaccine hesitancy rate was 19.5%. The main reasons for willingness to vaccinate included understanding the nature of disease and role of vaccination, in addition to information provided by physicians. Fears mainly centered around vaccine safety. Vaccine hesitators were more likely to be non-Qatari and having received the influenza vaccine at least once. Gender, marital status, socioeconomic status, educational level, and having completed childhood vaccinations were not associated with vaccine hesitancy.

Efforts should be directed toward raising awareness of vaccine efficacy and safety profiles. Physicians should additionally be educated about their pivotal role in advocating vaccine acceptance. We recommend reassessing vaccine hesitancy and its associated factors following a year of campaigning and vaccine administration to identify and target vulnerable groups.
Anticoagulation after transjugular intrahepatic portosystemic shunt for portal hypertension: A systematic review and meta analysis
Authors: Jiao Pan , Chen Xu-Ying , Zheng Hong-Yan , Qin Jia , Li Chao , Zhang Xiao-Lin
Published: June 2022

Background:

Transjugular intrahepatic portosystemic shunt (TIPS) is widely applied to decrease portal hypertension. Because of the lack of strong evidence, it is controversial whether anticoagulation should be performed after TIPS. This meta-analysis aimed to assess the safety and efficacy of anticoagulation for patients with portal hypertension following TIPS.

Methods:

Studies making comparisons between combination treatment and TIPS alone were searched in China National Knowledge Infrastructure, Cochrane Library, PubMed, the Wan Fang electronic databases, and EMBASE, delivered between the earliest accessible date and September 4, 2021. The RevMan version 5.3 was applied to conduct all statistical analyses. I2 index statistic was used to assess heterogeneity.

Results:

Five eligible studies were selected, and total 707 patients were enrolled. According to the meta-analysis, compared to TIPS alone, TIPS + anticoagulation led to much lower incidence of portal vein thrombosis (PVT; odds ratio [OR] = 0.39, 95% confidence interval [CI] 0.18–0.84, P = .02) as well as low heterogeneity (P = 0.36, I2 = 3%). Other index like the stent dysfunction rate (OR = 1.27, 95% CI 0.71–2.77, P = .42), bleeding rate (OR = 1.27, 95% CI 0.71–2.77, P = .42), and incidence of hepatic encephalopathy (OR = 0.87, 95% CI 0.56–1.36, P = .55) showed no statistical significance.

Conclusions:

In certain patients with portal hypertension, anticoagulation following TIPS may not be required. However, for patients who do not have a PVT before TIPS, post-TIPS anticoagulation can decrease the incidence of PVT. Nonetheless, further research is still required.
Identification of prognostic and immunotherapy-related eRNA ID2-AS1 in bladder cancer
Authors: Zhang Lei , Ding Degang , Liu Jianjun , Liu Junfeng , Wang Ning , Liu Jie
Published: June 2022

AbstractEnhancer RNAs (eRNAs) can participate in enhancer regulation and target gene transcription, thus affecting the occurrence and development of tumors. In this study, we identified eRNAs closely related to bladder cancer (BLCA).

Gene expression profiles and clinical information from The Cancer Genome Atlas (TCGA) database were used in this study. The Atlas of Noncoding RNAs in Cancer (TANRIC) co-expression data was also studied to evaluate correlations between the inferred levels of eRNA and its predicted target genes. Moreover, we evaluated differences in tumor microenvironment between high and low ID2-AS1 expression groups, and predicted the response of high- and low-expression groups to immune checkpoint inhibitor (ICI) treatment. Finally, we analyzed the prognostic value of ID2-AS1 in different tumors.

ID2-AS1 and ID2 were identified as eRNAs and target genes related to the prognosis of BLCA. Low ID2-AS1 levels were associated with advanced age, low overall survival, high histological grade, and late BLCA staging. ID2-AS1 appeared to regulate epithelial mesenchymal transition, mitotic spindle assembly, and angiogenesis, thereby affecting BLCA progression. The ID2-AS1 high-expression group had better ICI treatment response. In addition, ID2-AS1 also had prognostic value in other cancers.

ID2-AS1 helps predict prognostic and immunotherapeutic effects in BLCA.
LRP1B mutation associates with increased tumor mutation burden and inferior prognosis in liver hepatocellular carcinoma
Authors: Yu Ge , Mu Han , Fang Feng , Zhou Hongyuan , Li Huikai , Wu Qiang , Xiong Qingqing , Cui Yunlong
Published: June 2022

Background:

Liver hepatocellular carcinoma (LIHC) is the most common primary liver cancer and the main cause of death in patients with cirrhosis. LRP1B is found to involve in a variety of cancers, but the association of LRP1B mutation with tumor mutation burden (TMB) and prognosis of LIHC is rarely studied.

Methods and Results:

Herein, we analyzed the somatic mutation data of 364 LIHC patients from The Cancer Genome Atlas (TCGA) and found that LRP1B showed elevated mutation rate. Calculation of the TMB in LRP1B mutant and LRP1B wild-type groups showed that LRP1B mutant group had higher TMB compared with that in LRP1B wild-type group. Then survival analysis was performed and the survival curve showed that LRP1B mutation was associated with poor survival outcome, and this association remained to be significant after adjusting for multiple confounding factors including age, gender, tumor stage, mutations of BRCA1, BRCA2, and POLE.

Conclusion:

Collectively, our results revealed that LRP1B mutation was related to high TMB value and poor prognosis in LIHC, indicating that LRP1B mutation is probably helpful for the selection of immunotherapy and prognosis prediction in LIHC.