bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding the Immunophenotype Spectrum of SMARCA4-Deficient Non-Small Cell Lung Carcinomas: A Case Series with Neuroendocrine Markers Expression
Authors: Mao Ruiqi , Liu Min , Shu Xiangfang , Li Wenli , Yan Wei , Li Xinjun
Published: October 2021

Aims. In recent years, SMARCA4-deficient nonsmall cell lung cancer (NSCLC) has been recognized as a distinct new subtype of lung cancer, which is characterized by loss of SMARCA4 (Brahma-related gene-1 [BRG1]) protein expression. Only a limited number of SMARCA4-deficient NSCLC case series have been reported, and their clinicopathological features have not yet been fully elucidated. Our main aim was to analyze the clinical history, histology, immunohistochemistry, and molecular pathology of 5 SMARCA4-deficient NSCLC patients with poorly differentiated or undifferentiated histology and neuroendocrine markers expression. Methods and results. Five patients with complete loss of nuclear BRG1 immunostaining were identified among 53 patients of poorly differentiated/undifferentiated NSCLC. We then performed immunohistochemical staining and gene mutation analysis using a real-time polymerase chain reaction. All patients were male aged between 58 and 82 years (average 67.6 years), with smoking exposure. Histologically, the tumors had a relatively monotonous morphology and showed solid nest-like, sheet-like growth, and geographic necrosis. Thyroid transcription factor 1, cytokeratin 7, and Napsin A were all negative (5 of 5). Moreover, all tumors showed a variable expression of neuroendocrine markers, including synaptophysin, chromogranin A and CD56. Hot spot epidermal growth factor receptor/anaplastic large-cell lymphoma kinase/c-ros oncogene 1 mutations were not detected in any of the 5 tumors. Conclusions. To the best of our knowledge, this is the first study that has reported the poorly differentiated morphology with a frequent expression of neuroendocrine markers. Our results have expanded the immunophenotype spectrum of SMARCA4-deficient NSCLC. However, the clinicopathological significance of this subset of SMARCA4-deficient NSCLC should be further clarified in larger series studies.
Discharge Communications for Older Patients Between Hospital Healthcare Providers and Home Healthcare Providers: An Integrative Review
Authors: Kim Yeonsu , Crandall Mary , Byon Ha Do
Published: October 2021

The increasing volume of our aging population is dramatically affecting the need for home care services. The discharge process from hospital to home can be fraught with communication challenges if critical information is not provided. The transition process can threaten patient safety and incur adverse patient health outcomes. However, little is known about how the communication occurs between hospital and home health providers. Therefore, this integrative literature review was conducted to (1) describe the discharge communication that is occurring for older patients between hospital and home healthcare providers and (2) summarize the limitations of current discharge communication. A systematic search was conducted using CINAHL, PubMed, Web of Science, and PsycINFO databases. Findings were categorized to address each aim. Seven studies were included for full reviews. Healthcare providers used a variety of communication methods, including: written information, phone calls, or in-person meetings to exchange the discharge information of older patients. Limitations in communications included excessive and incomplete discharge documents, lack of provider’s contact information, lack of trust in each other, and lack of bidirectional communications. The quality of discharge communications can improve by utilizing mediators and implementing standardized discharge documentation requirements. Overall, there was a lack of literature that described the methods and limitations of discharge communication for older patients between hospital and home care services. Further studies can be conducted to generate more evidence. Healthcare providers may improve the quality of discharge communication by addressing the suggested areas.
Advancing the Care of Pancreatic Cancer Patients: Moving Beyond Just Tumour Tissue
Authors: Kalloger Steve E , Karasinska Joanna M , Warren Cassia , Renouf Daniel J , Schaeffer David F
Published: October 2021

Biobanking efforts, to establish and grow the pool of available tissue from which evidence on aetiology, therapeutic susceptibility and prognosis of various diseases, have been underway for decades. This is illustrated nowhere better than in cancer. High incidence cancers such as breast, colorectal and lung have seen massive increases in their requisite formularies that have yielded improved prognoses. These discoveries, on a very fundamental level, were made by scientists who had access to tumour tissue and associated clinical data from patient donors. As the research space for higher incidence malignancies became increasingly crowded, attention has turned towards those malignancies with lower incidence. In the same time span, technology has continued to evolve, allowing the next generation of scientists and clinicians to ask more nuanced questions. Inquiries are no longer limited to the -omics of tumour tissue but also include biomarkers of blood and excretory products, concurrent disease status and composition of the gut microbiome. The impact of these new technologies and the questions now facing researchers in low-incidence cancers will be summarized and discussed. Our experience with pancreatic ductal adenocarcinoma will be used as a model for this review.
Effects of Psychological and Physical Stress on Oxidative Stress, Serotonin, and Fatigue in Young Females Induced by Objective Structured Clinical Examination: Pilot Study of u-8-OHdG, u-5HT, and s-HHV-6
Authors: Iida Tadayuki , Ito Yasuhiro , Kanazashi Miho , Murayama Susumu , Miyake Takashi , Yoshimaru Yuki , Tatsumi Asami , Ezoe Satoko
Published: October 2021

Background:

To establish a method to prevent and manage fatigue caused by psychological and physical stress in young females, early detection factors, such as understanding of fatigue and causes of psychological and physical stress, as well as a review of early management of psychiatric disease, are important. With increasing knowledge regarding the diverse causes of stress, it is important to select biomarkers with consideration of the types of stress burden and mechanisms underlying the development of physical symptoms. The methods used to search for stress characteristics is an issue that needs to be addressed. However, consensus regarding objective assessment methods for impaired mental health is lacking.

Methods:

We examined the effects of an objective structured clinical examination (OSCE), considered to be a uniform source of psychological and physical stress, on biomarkers of oxidative stress and fatigue in 16 third-year female medical university students (21.3 ± 2.1 years old) in Japan with a normal menstrual cycle. A self-administered questionnaire consisting of Zung’s Self-rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI) was used to assess subjective stress. Furthermore, stress-related biomarkers (urinary 8-hydroxy-2ʹ-deoxyguanosine [u-8-OHdG], urinary 5-hydroxytryptamine [u-5-HT], and salivary human herpesvirus-6 [s-HHV-6]) were examined at 1 month, 1 week, and 1 day before, and 1 week after the OSCE.

Results:

The results indicated that the OSCE did not have effects on u-8-OHdG, a biomarker of oxidative stress. However, u-5-HT and s-HHV-6 were found to be elevated in examinations performed prior to the OSCE.

Conclusions:

The present findings suggest that u-5-HT and s-HHV-6 levels can be used for objective assessment of mental and physical fatigue in young females, including that produced not only by knowledge regarding an upcoming OSCE, but also by skill and attitude aspects related to that examination.
Biochemical Stress Markers, Antioxidants, and Infectious Wound-Healing Potential of UV Irradiation and Salt Stress Effects on the Pre-Treated Seed of Bitter Melon (Momordica charantia L.)
Authors: Abbas Mazhar , Sharif Sumaira , Baig Ibrahim Salam , Anjum Rimsha , Riaz Muhammad , Rafique Muhammad Kamran , Rahman Abdur , Nazish Nadia , Al-Mijalli Samiah H. , Iqbal Munawar
Published: October 2021

Purpose

The secondary metabolites in plants are the basis of defense and stress balance, which is an important aspect in plant growth. The UV-B treatment (a biotic stress) and salt stress on bitter melon ( Momordica charantia L.) were studied, and the impact of pre-sowing seed treatment was evaluated on the basis of biochemical and enzymatic biomarkers, antioxidants, and wound-healing potential during early growth stages.

Methods

The UV-B treatment for 5 and 10 min and salt stress 250 mM and 500 mM treatments were applied, and 21-day seedling tissue were collected for total phenolic contents (TPC), total flavonoid contents (TFC), antioxidant, chlorophyll contents, hydrogen peroxide, total soluble sugar, enzymes activities, and wound-healing potential studies.

Results

The TPC, TFC, diphenyl picrylhydrazyl (DPPH), chlorophyll contents, and total soluble sugar were recorded higher at 5 min treatment with UV-B and salt stress at 250 mM concentration. Antioxidant enzymes activities were recorded higher for 10 min UV-B treatment and 500 mM salt treatment. Wound-healing potential was found significant at 5 min treatment with UV-B radiation, which was studied in vivo in rabbits. The LC-MS analysis revealed a variety of phenolic compounds in the seedlings.

Conclusion

The study concluded that treatments significantly affect the biological activities of bitter melon seeds at the seedling stage, and the seeds contain important phenolic compounds responsible for its antioxidant potential and enzymatic activities. Future studies could be focused on the later stages of growth, development, and yield characteristics subjected to salt stress along with UV-B radiation treatment.
Coix Seed May Affect Human Immune Function
Authors: Suzuki Yoshio , Konaya Yohei
Published: October 2021

Coix ( Coix lacryma-jobi Linné . var . mayuen Stapf) is, unlike many herbs used in Chinese traditional medicines, often used as a single agent. Coix seed has its specific constituents coixenolide and coixol. This review summarizes the effects of coix seed on human pathology and physiology, and the roles of coixenolide and coixol on the effects. The comprehensive literature search was conducted using PubMed, Citation Information by National Institute of Informatics of Japan (CiNii), University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), and ClinicalTrials.gov databases. Some studies suggest that coix seed promotes the spontaneous regression of viral infections of the skin. Meanwhile, kanglite, a purified oil agent used for cancer therapy, has been implied to increase the ratio of CD4 + T cells in the peripheral blood of cancer patients undergoing treatment. These studies seem to indicate that coix seed may affect cellular immune function. However, there are limitations to the individual studies on which the above consideration is based, and thereby, it is not conclusive what specific immune or clinical indices coix seed affects. In addition, the effects of coixol on human immune function have not been clarified. Therefore, coix seed seems promising for health promotion and presents a challengeable and attractive theme for natural product chemists, pharmacologists, immunologists, and clinicians.
Anxiety and depressive symptoms among COVID-19 patients admitted to three isolation facilities in Bangladesh
Authors: Rahman Md Hafizur , Banik Goutom , Ahmed Anisuddin , Arifeen Shams El , Hossain Aniqa Tasnim , Hasan Md Aminul , Rahman Ahmed Ehsanur
Published: October 2021

The COVID-19 pandemic can impose a profound impact on the mental health of hospitalised patients infected with SARS-CoV-2. However, there have been no studies that explored the psychological distress of the COVID-19 inpatients in Bangladesh. Therefore, this study aimed to assess the prevalence of anxiety and depressive symptoms and explore the associated factors among inpatients with COVID-19. A cross-sectional study was conducted among 138 COVID-19 patients admitted to three isolation facilities in Dhaka, Bangladesh, from September to October 2020. Participants’ sociodemographic and clinical data were obtained. Mental health symptoms were evaluated with the Hospital Anxiety and Depression Scale (HADS). Descriptive statistics, bivariate and multivariate logistic regression models were performed to analyse the data. The prevalence of anxiety and depressive symptoms were 57.2% (95% CI: 48.2–65.2) and 52.2% (95% CI: 43.8–62.7), respectively. Presence of comorbidity (aOR: 5.64, 95% CI: 2.21–14.35) and having ≥3 COVID-19 physical symptoms (aOR: 6.90, 95% CI: 2.71–17.56) were associated with anxiety symptoms. Besides, presence of comorbidity (aOR: 2.73, 95% CI: 1.07–6.99), having ≥3 COVID-19 physical symptoms (aOR: 4.46, 95% CI: 1.78–11.20) and patient with ≤93% oxygen saturation (aOR: 2.33, 95% CI: 1.01–5.36) were associated with depressive symptoms. Considerable numbers of COVID-19 patients in Bangladesh experienced psychological distress during hospitalisation, requiring more attention and timely mental health interventions.
Steroids plus antiviral agents are more effective than steroids alone in the treatment of severe Bell’s palsy patients over 40 years of age
Authors: Kim Yong , Doo Jeon Gang , Chon Jinmann , Lee Jong Ha , Jung Junyang , Lee Jae Min , Kim Sang Hoon , Yeo Seung Geun
Published: October 2021

Objective

The effectiveness of the combination of steroids and antiviral agents in the treatment of Bell’s palsy remains unclear. This study evaluated the therapeutic effect of combination therapy in severe Bell’s palsy patients and assesses specific conditions under which combination therapy is more effective than steroids alone.

Methods

From January 2005 to December 2019, the records of 1710 Bell’s palsy patients who visited Kyung Hee University Hospital were reviewed retrospectively. Of these, 335 (19.6%) patients were diagnosed with severe Bell’s palsy, with 162 patients treated with steroids alone and 173 patients treated with combinations of steroids and antiviral agents. The outcomes of treatment were assessed using the House–Brackmann (H-B) grade according to age, sex, hypertension, diabetes, and obesity.

Results

The favorable recovery rate was significantly higher in severe Bell’s palsy patients who were treated with combinations of steroids and antiviral agents than with steroids alone (78.0% vs. 66.7%, p = 0.020). Subgroup analysis showed that combination therapy resulted in significantly higher recovery rates than steroids alone in patients aged ≥40 years (77.5% vs. 64.1%, p = 0.023) and in those without hypertension (75.8% vs. 63.3%, p = 0.044) and diabetes (79.7% vs. 65.5%, p = 0.007).

Conclusion

Combination therapy with steroids and antiviral agents resulted in significantly higher favorable recovery rates than steroids alone in severe Bell’s palsy patients. Combination therapy was particularly more effective than steroids alone in patients aged ≥40 years and in patients without hypertension and diabetes.
Estradiol attenuates LPS-induced acute lung injury via induction of aquaporins AQP1 and AQP5
Authors: Wang Xiaobo , Zhou Xiuyun , Xia Xiumei , Zhang Yili
Published: October 2021

Background

Acute lung injury (ALI) is associated with increased inflammation and oxidative stress. Estradiol is produced by the ovaries and is the most active hormone of estrogen. Our aim was to investigate whether estradiol contributes to protect against lipopolysaccharide (LPS)-induced ALI via induction of aquaporins AQP1 and AQP5 and the underlying mechanisms. Methods and results For induction of ALI, LPS was applied once by intraperitoneal injection in SD rats 14 days after oophorectomy. To assess the therapeutic effects of estradiol on LPS-induced ALI, estradiol was subcutaneously injected for 1 h prior to LPS challenge. Estradiol can significantly attenuate the lung edema reflected by decreasing wet-to-dry weight ratio and permeability of lung and total protein concentration of bronchial lavage fluid (BALF). Results of histological detection showed that estradiol attenuated the lung injury reflected by reducing edema, congestion, and thickening pulmonary septal of lung tissues. In addition, estradiol attenuated TNF-α, IL-1β, and IL-6 and oxidative stress in lung tissues. Estradiol was more effective than estradiol associated with ERα antagonist or ERβ antagonist in protecting against LPS-induced ALI in rats. Mechanistically, we investigate whether estradiol regulates the expression of AQP1 and AQP5 in lung tissues. Of interest, estradiol upregulates AQP1 and AQP5 mRNA and protein expression. Taken together, these results demonstrate that estradiol can increase the expression of AQP1 and AQP5, which plays a critical role in ameliorating oxidative stress and downregulating inflammatory responses induced by LPS.Conclusion Therefore, these findings strongly suggest that AQP1 and AQP5 mediate the anti-inflammatory and antioxidant effects of estradiol.
Awareness and Use of the Sickle Cell Disease Toolbox by Primary Care Providers in North Carolina
Authors: Ibemere Stephanie O. , Tanabe Paula , Bonnabeau Emily , Rains Gary , Eason Kern , Earls Marian F. , Shah Nirmish
Published: October 2021

Background

Sickle cell disease (SCD) is a complex chronic blood disorder characterized by severe disease complications ideally managed by both hematologists and primary care providers (PCP’s). PCP’s report knowledge gaps and discomfort with SCD management. Our team developed and a decision support tool for SCD management (SCD Toolbox) based on the National Heart, Lung, and Blood Institute’s SCD guidelines. We surveyed PCPs in North Carolina (NC) prior to formal dissemination to determine current co-management practices, assess toolbox acceptability, use, format preferences, and understand which algorithms would be most helpful.

Method

A 23-item baseline needs assessment survey was disseminated to PCPs throughout NC.

Results

A total of 63 medical providers responded to the survey and of these respondents, 64% reported caring for 1 to 10 patients with SCD. Only 39% of PCPs reported regular communication with an SCD specialist. Providers reported the highest level of awareness of the pediatric and adult health maintenance tools (41% and 39% respectively) and highest use of the pediatric (26%) and adult (28%) health maintenance tools. Respondents also expressed a desire to have access to multiple toolbox formats (37%) (website, mobile app and/or paper).

Limitations

The use of a convenience sample and low survey response are study limitations which hinder generalizability.

Conclusions

PCPs rarely co-managed with a specialist, had low awareness and use of SCD toolbox, and requested multiple formats for the toolbox.
Consumer Response to Patriotic Ads for Domestic Versus Foreign Brands in Contexts of International Sporting Events: The Role of National Identity Activation and Group Emotion
Authors: Yoo Jinyoung Jinnie , Choi Dongwon , Bang Hyejin
Published: October 2021

An individual possesses multiple social identities, and different identities are temporarily salient at different points in time. A particular social identity, such as national identity (NI), may have little or no impact on consumer response unless that identity is activated. This study explores how NI activated through different contexts of international sporting events and associated group-based emotions (happiness vs. anger) would exert differential influence on consumers’ responses to patriotic ads. Further, this study proposes that this effect would vary depending on the corporate origin of the brand, which refers to whether the advertised brand is domestic or foreign. Findings show that (1) while both happiness and anger improve consumer responses to patriotic ads, such an effect is significantly stronger in the happiness-eliciting context, and (2) while NI activation in the happiness-eliciting context has an effect on increasing consumers’ responses to patriotic ads regardless of the corporate origin of the brands, the effect of activating NI is greater for a domestic (vs. foreign) brand in the anger-eliciting context. This study contributes to extending previous findings by applying two important variables—contexts of activating NI that elicit specific group-based emotions and a corporate origin of the brand—that influence consumer response to a patriotic ad.
An Interprofessional Team-Based Experiential Learning Experience in Public Libraries
Authors:   Stony Brook Medicine Healthy Libraries Laboratory (HLL), Pandolfelli Gabriella , Hammock Amy , Topek-Walker Leah , D’Ambrosio Matthew , Tejada Talissa , Della Ratta Carol , LaSala Mary Ellen , Koos Jessica A. , Lewis Valerie , Benz Scott Lisa
Published: October 2021

The Stony Brook Medicine Healthy Libraries Program (HeLP) is an interprofessional team-based experiential learning opportunity for health professional students. University faculty members in the fields of nursing, public health, social work, and library science collaborated with four suburban public library directors to design, implement, and evaluate a team-based interprofessional service-learning experience, in which supervised students engaged in health monitoring and promotion in the library setting. Participating students were enrolled in either a semester-long population health course ( n = 16), a Master of Social Work fieldwork internship ( n = 2), a Master of Library Science internship ( n = 1), or a Master of Public Health practicum ( n = 2). HeLP faculty educated students on content, library culture, communication, professional roles/responsibilities, and documentation using standardized data collection tools. Concurrently, the interprofessional student teams delivered resources to patrons 1 day a week, with alternating locations, for a minimum of 2 hours per visit over the course of 6 weeks. HeLP provided students with an opportunity to apply core competencies based on the Interprofessional Education Collaborative. The team-based approach fostered interprofessional learning, as students worked together to assist library patrons on health and social needs. Throughout the program’s duration, students documented the type of resources provided, the types of encounters between team members, and the number of referrals. Student learning was assessed after program completion using three open-ended reflection questions.
Early detection of WT1 measurable residual disease identifies high-risk patients, independent of transplantation in AML
Authors: Lambert Juliette , Lambert Jerome , Thomas Xavier , Marceau-Renaut Alice , Micol Jean-Baptiste , Renneville Aline , Clappier Emmanuelle , Hayette Sandrine , Récher Christian , Raffoux Emmanuel , Pigneux Arnaud , Berthon Celine , Terré Christine , Celli-Lebras Karine , Castaigne Sylvie , Boissel Nicolas , Rousselot Philippe , Preudhomme Claude , Dombret Hervé , Duployez Nicolas
Published: October 2021

WT1 overexpression is frequently identified in acute myeloid leukemia (AML) and has been reported to be a potential marker for monitoring measurable residual disease (MRD). We evaluated the use of postinduction WT1 MRD level as a prognostic factor, as well as the interaction between postinduction WT1 MRD response and the effect of allogeneic stem cell transplantation (allo-SCT) in the first complete remission (CR). In the ALFA-0702 trial, patients with AML, aged 18 to 59, had a prospective quantification of WT1 MRD. The occurrence of a WT1 MRD ratio >2.5% in bone marrow or >0.5% in peripheral blood was defined as MRDhigh, and ratios below these thresholds were defined as MRDlow. The prognostic value of MRD after induction chemotherapy was assessed in 314 patients in first CR by comparing the risk of relapse, the relapse-free survival (RFS), and the overall survival (OS). Interaction between MRD response and the allo-SCT effect was evaluated in patients by comparing the influence of allo-SCT on the outcomes of patients with MRDhigh with those with MRDlow. The results showed that patients with MRDhigh after induction had a higher risk of relapse and a shorter RFS and OS. The MRD response remained of strong prognostic value in the subset of 225 patients with intermediate-/unfavorable-risk AML who were eligible for allo-SCT, because patients with MRDhigh had a significantly higher risk of relapse resulting in worse RFS and OS. The effect of allo-SCT was higher in patients with MRDlow than in those with MRDhigh, but not significantly different. The early WT1 MRD response highlights a population of high-risk patients in need of additional therapy.
Metabolic adaptation drives arsenic trioxide resistance in acute promyelocytic leukemia
Authors: Balasundaram Nithya , Ganesan Saravanan , Chendamarai Ezhilarasi , Palani Hamenth Kumar , Venkatraman Arvind , Alex Ansu Abu , David Sachin , Kumar Swathy Palani , Radhakrishnan Nair Reeshma , Yasar Mohammed , Krishna Sanjeev , Korula Anu , Kulkarni Uday , Janet Nancy Beryl , Balasubramanian Poonkuzhali , Mathews Vikram
Published: October 2021

Acquired genetic mutations can confer resistance to arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL). However, such resistance-conferring mutations are rare and do not explain most disease recurrence seen in the clinic. We have generated stable ATO-resistant promyelocytic cell lines that are less sensitive to all-trans retinoic acid (ATRA) and the combination of ATO and ATRA compared with the sensitive cell line. Characterization of these resistant cell lines that were generated in-house showed significant differences in immunophenotype, drug transporter expression, anti-apoptotic protein dependence, and promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) mutation. Gene expression profiling revealed prominent dysregulation of the cellular metabolic pathways in these ATO-resistant APL cell lines. Glycolytic inhibition by 2-deoxyglucose (2-DG) was sufficient and comparable to the standard of care (ATO) in targeting the sensitive APL cell line. 2-DG was also effective in the in vivo transplantable APL mouse model; however, it did not affect the ATO-resistant cell lines. In contrast, the resistant cell lines were significantly affected by compounds targeting mitochondrial respiration when combined with ATO, irrespective of the ATO resistance-conferring genetic mutations or the pattern of their anti-apoptotic protein dependency. Our data demonstrate that combining mitocans with ATO can overcome ATO resistance. We also show that this combination has potential for treating non-M3 acute myeloid leukemia (AML) and relapsed APL. The translation of this approach in the clinic needs to be explored further.
Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma
Authors: Pighi Chiara , Cheong Taek-Chin , Compagno Mara , Patrucco Enrico , Arigoni Maddalena , Olivero Martina , Wang Qi , López Cristina , Bernhart Stephan H. , Grande Bruno M. , Poggio Teresa , Langellotto Fernanda , Bonello Lisa , Dall’Olio Riccardo , Martínez-Martín Sandra , Molinaro Luca , Francia di Celle Paola , Whitfield Jonathan R. , Soucek Laura , Voena Claudia , Calogero Raffaele A. , Morin Ryan D. , Staudt Louis M. , Siebert Reiner , Zamò Alberto , Chiarle Roberto
Published: October 2021

The expression of BCL6 in B-cell lymphoma can be deregulated by chromosomal translocations, somatic mutations in the promoter regulatory regions, or reduced proteasome-mediated degradation. FBXO11 was recently identified as a ubiquitin ligase that is involved in the degradation of BCL6, and it is frequently inactivated in lymphoma or other tumors. Here, we show that FBXO11 mutations are found in 23% of patients with Burkitt lymphoma (BL). FBXO11 mutations impaired BCL6 degradation, and the deletion of FBXO11 protein completely stabilized BCL6 levels in human BL cell lines. Conditional deletion of 1 or 2 copies of the FBXO11 gene in mice cooperated with oncogenic MYC and accelerated B-cell lymphoma onset, providing experimental evidence that FBXO11 is a haploinsufficient oncosuppressor in B-cell lymphoma. In wild-type and FBXO11-deficient BL mouse and human cell lines, targeting BCL6 via specific degraders or inhibitors partially impaired lymphoma growth in vitro and in vivo. Inhibition of MYC by the Omomyc mini-protein blocked cell proliferation and increased apoptosis, effects further increased by combined BCL6 targeting. Thus, by validating the functional role of FBXO11 mutations in BL, we further highlight the key role of BCL6 in BL biology and provide evidence that innovative therapeutic approaches, such as BCL6 degraders and direct MYC inhibition, could be exploited as a targeted therapy for BL.
Urban mosquitoes and filamentous green algae: their biomonitoring role in heavy metal pollution in open drainage channels in Nairobi industrial area, Kenya
Authors: Kinuthia Geoffrey Kariuki , Ngure Veronica , Kamau Luna
Published: October 2021

Background

Industrial wastewater is a human health hazard upon exposure. Aquatic organisms in contaminated wastewater may accumulate the toxic elements with time. Human population living in informal settlements in Nairobi industrial area risk exposure to such toxic elements. Biomonitoring using aquatic organisms in open drainage channels can be key in metal exposure assessment. Levels of Mercury (Hg), Lead (Pb), Chromium (Cr), Cadmium (Cd), Thallium (Tl), and Nickel (Ni) were established in samples of wastewater, filamentous green algae (Spirogyra) and mosquitoes obtained from open drainage channels in Nairobi industrial area, Kenya.

Results

Pb, Cr, & Ni levels ranged from 3.08 to 15.31 µg/l while Tl, Hg, & Cd ranged from 0.05 to 0.12 µg/l in wastewater. The Pb, Cr, Ni, & Cd levels were above WHO, Kenya & US EPA limits for wastewater but Hg was not. Pb, Cr, Tl, & Ni levels in assorted field mosquitoes were 1.3–2.4 times higher than in assorted laboratory-reared mosquitoes. Hg & Cd concentrations in laboratory-reared mosquitoes (0.26 mg/kg & 1.8 mg/kg respectively) were higher than in field mosquitoes (0.048 mg/kg & 0.12 mg/kg respectively). The levels of Pb, Cr, & Ni were distinctively higher in field mosquito samples than in wastewater samples from the same site. Pb, Cr, Ni, Cd & Hg levels in green filamentous Spirogyra algae were 110.62, 29.75, 14.45, 0.44, & 0.057 mg/kg respectively. Correlation for Pb & Hg (r (2) = 0.957; P < 0.05); Cd & Cr (r (2) = 0.985; P < 0.05) in algae samples was noted. The metal concentrations in the samples analyzed were highest in filamentous green algae and least in wastewater.

Conclusion

Wastewater, mosquitoes, and filamentous green algae from open drainage channels and immediate vicinity, in Nairobi industrial area (Kenya) contained Hg, Pb, Cr, Cd, Tl, and Ni. Mosquitoes in urban areas and filamentous green algae in open drainage channels can play a role of metal biomonitoring in wastewater. The potential of urban mosquitoes transferring heavy metals to human population from the contaminated wastewater should be investigated.
Ecology impacts the decrease of Spirochaetes and Prevotella in the fecal gut microbiota of urban humans
Authors: Thingholm Louise B. , Bang Corinna , Rühlemann Malte C. , Starke Annika , Sicks Florian , Kaspari Verena , Jandowsky Anabell , Frölich Kai , Ismer Gabriele , Bernhard Andreas , Bombis Claudia , Struve Barbara , Rausch Philipp , Franke Andre
Published: October 2021

Compared to the huge microbial diversity in most mammals, human gut microbiomes have lost diversity while becoming specialized for animal-based diets – especially compared to chimps, their genetically closest ancestors. The lowered microbial diversity within the gut of westernized populations has also been associated with different kinds of chronic inflammatory diseases in humans. To further deepen our knowledge on phylogenetic and ecologic impacts on human health and fitness, we established the herein presented biobank as well as its comprehensive microbiota analysis. In total, 368 stool samples from 38 different animal species, including Homo sapiens, belonging to four diverse mammalian orders were collected at seven different locations and analyzed by 16S rRNA gene amplicon sequencing. Comprehensive data analysis was performed to (i) determine the overall impact of host phylogeny vs. diet, location, and ecology and to (ii) examine the general pattern of fecal bacterial diversity across captive mammals and humans.

By using a controlled study design with captive mammals we could verify that host phylogeny is the most dominant driver of mammalian gut microbiota composition. However, the effect of ecology appears to be able to overcome host phylogeny and should therefore be studied in more detail in future studies. Most importantly, our study could observe a remarkable decrease of Spirochaetes and Prevotella in westernized humans and platyrrhines, which is probably not only due to diet, but also to the social behavior and structure in these communities.

Our study highlights the importance of phylogenetic relationship and ecology within the evolution of mammalian fecal microbiota composition. Particularly, the observed decrease of Spirochaetes and Prevotella in westernized communities might be associated to lifestyle dependent rapid evolutionary changes, potentially involved in the establishment of dysbiotic microbiomes, which promote the etiology of chronic diseases.
Practices and perspectives of primary care physicians in Japan and the United States about diagnosing dementia: a qualitative study
Authors: Abe M. , Tsunawaki S. , Dejonckheere M. , Cigolle C. T. , Phillips K. , Rubinstein E. B. , Matsuda M. , Fetters M. D. , Inoue M.
Published: October 2021

Background

While dementia is a common problem in Japan and the US, primary care physicians' practices and perspectives about diagnosing dementia in these different healthcare systems are unknown.

Methods

Qualitative research was conducted in an ethnographic tradition using semi-structured interviews and thematic analysis in primary care settings across Japan and in the Midwest State of Michigan, US. Participants were a total of 48 primary care physicians, 24 each from Japan and the US participated. Both groups contained a mixture of geographic areas (rural/urban), gender, age, and years of experience as primary care physicians.

Results

Participants in Japan and the US voiced similar practices for making the diagnosis of dementia and held similar views about the desired benefits of diagnosing dementia. Differences were found in attitudes about the appropriate timing of formally diagnosing dementia. Japanese physicians tended to make a formal diagnosis when problems that would benefit from long-term care services emerged for family members. US physicians were more proactive in diagnosing dementia in the early stages by screening for dementia in health check-ups and promoting advance directives when the patients were still capable of decision-making. Views about appropriate timing of diagnostic testing for dementia in the two systems reflect what medical or nursing care services physicians can use to support dementia patients and caregivers.

Conclusions

Benefits of making the diagnosis included the need to activate the long-term care services in Japan and for early intervention and authoring advance directives in the US. Testing to establish an early diagnosis of dementia by primary care physicians only partly relates to testing and treatment options available. Benefits of making the diagnosis included the need to activate the long-term care services in Japan and for early intervention and authoring advance directives in the US.
The resurgence of yellow fever outbreaks in Nigeria: a 2-year review 2017–2019
Authors: Nomhwange Terna , Jean Baptiste Anne Eudes , Ezebilo Obi , Oteri Joseph , Olajide Lois , Emelife Kizito , Hassan Shehu , Nomhwange Erdoo R. , Adejoh Kennedy , Ireye Faith , Nora Eyo E. , Ningi Adamu , Bathondeli Blaise , Tomori Oyewale
Published: October 2021

Background

Yellow fever outbreaks are documented to have a considerable impact not only on the individuals but on the health system with significant economic implications. Efforts to eliminate yellow fever outbreaks globally through the EYE strategy remains important following outbreaks in Africa, Nigeria included. The outbreaks reported in Nigeria, since 2017 and the response efforts provide an opportunity to document and guide interventions for improving future outbreaks in Nigeria and other countries in Africa.

Methods

We reviewed the available yellow fever surveillance and vaccination response data between September 2017 and September 2019 across the 36 states across Nigeria. We described the epidemiology of the difference outbreaks and the periods for all interventions. We also documented the emergency vaccination responses as well as preventive mass vaccinations implemented towards improving population immunity and limiting epidemic potentials in Nigeria.

Results

A total of 7894 suspected cases with 287 laboratory-confirmed cases were reported in Nigeria between September 2017 and September 2019 with a mean age of 19 years and a case fatality of 2.7% amongst all reported cases. Outbreaks were confirmed in 55 LGAs with most of the outbreaks across four major epicentres in Kwara/Kogi, Edo, Ebonyi and Bauchi states. In response to these outbreaks, eight reactive vaccination campaigns, supported through ICG applications, were implemented. The duration for responding to the outbreaks ranged from 15 to 132 days (average 68 days) and a total of 45,648,243 persons aged < 45 years vaccinated through reactive and preventive mass campaigns between September 2017 and September 2019.

Conclusions

Nigeria experienced intermediate outbreaks of yellow fever between September 2017 and 2019 with vaccination responses conducted to control these outbreaks. However, there are delays in the timeliness of responses and more efforts required in improving reporting, response times and preparedness to further prevent morbidity and mortality from the yellow fever disease outbreaks. These efforts, including improving routine yellow fever coverage, contribute towards improving population immunity and other activities related to achieving the goals of the EYE strategy.
Clinicopathological features and outcomes in gastric-type of HPV-independent endocervical adenocarcinomas
Authors: Chen Lili , Niu Yizhen , Wan Xiaoyun , Yu Lina , Zhang Xiaofei , Strickland Amanda Louise , Dong Liya , Zhou Feng , Lu Weiguo
Published: October 2021

Background

We aimed to analyze the clinicopathological features and outcomes of patients with gastric-type of HPV-independent endocervical adenocarcinoma (GAS HPVI ECA), and compare them with non-GAS HPVI ECA cases.

Methods

Thirty-eight GASs [including 17 minimal deviation adenocarcinoma (MDA), 21 non-MDA GAS] and 17 non-GAS HPVI ECAs were studied. Data of clinical features, pathological characteristics, treatment, and outcomes were evaluated.

Results

The median age of patients with GAS and non-GAS HPVI ECA was 46 and 48 years, respectively (p = 0.93). Compared with non-GAS HPVI ECAs, GAS had more common complains of vaginal watery discharge (p = 0.04). GAS cases were also associated with higher clinical stage (p = 0.036), more common in deeper cervical stromal invasion (p = 0.002) and lymphoavascular invasion (p = 0.044). GAS was associated with worse median progression-free survival (PFS) (p = 0.02) and median overall survival (OS) (p = 0.03) over patients with non-GAS HPVI ECAs. MDA had similar clinical and pathological features and prognosis compared with non-MDA GAS. Of note, serum CA19–9 levels were significantly higher in GAS than that in non-GAS HPVI ECA cases.

Conclusions

GAS cases were more likely to have high risk pathological factors and poorer PFS and OS compared with non-GAS HPVI ECAs. Serum CA19–9 may be helpful for diagnosis and screening in patients with GAS.
Hybrid versus total sublaminar wires in patients with spinal muscular atrophy undergoing scoliosis surgery
Authors: Chou Shih-Hsiang , Li Wen-Wei , Lu Cheng-Chang , Lin Kun-Ling , Lin Sung-Yen , Shen Po-Chih , Tien Yin-Chun , Huang Hsuan-Ti
Published: October 2021

Background

Early versions of spinal muscular atrophy (SMA) scoliosis correction surgery often involved sublaminar devices. Recently, the utilization of pedicle screws has gained much popularity. Pedicle screws are generally believed to provide additional deformity correction, but pedicle size and rotational deformity limit their application in the thoracic spine, resulting in a hybrid construct involving pedicle screws and sublaminar wire. Studies of the efficacy of hybrid instrumentation in SMA scoliosis are often limited by the scarcity of the disease itself. In this study, we aimed to compare the surgical outcomes between hybrid constructs involving pedicle screws and sublaminar wire and sublaminar wire alone in patients with SMA scoliosis.

Methods

We retrospectively reviewed the clinical records and radiographic assessments of patients with SMA scoliosis who underwent corrective surgery between 1993 and 2017. The radiographic assessments included deformity correction and progressive changes in the major curve angle, pelvic tilt (PT) and coronal balance (CB). The correction of deformities was observed postoperatively and at the patient’s 2-year follow-up to test the efficacy of each type of construct.

Results

Thirty-three patients were included in this study. There were 14 and 19 patients in the wiring and hybrid construct groups, respectively. The hybrid construct group demonstrated a higher major curve angle correction (50.5° ± 11.2° vs. 36.4° ± 8.4°, p < 0.001), a higher apical vertebral rotation correction (10.6° ± 3.9° vs. 4.8° ± 2.6°, p < 0.001), and a reduced progression of the major curve angle at the 2-year follow-up (5.1° ± 2.9° vs. 8.7° ± 4.8°, p < 0.001). A moderate correlation was observed between the magnitude of correction of the apical vertebral rotation angle and the major curve (r = 0.528, p = 0.002).

Conclusion

This study demonstrated that hybrid instrumentation can provide a greater magnitude of correction in major curve and apical rotation as well as less major curve progression than sublaminar wire instrumentation alone in patients with SMA scoliosis. Level of evidence III
The impact of a computerized physician order entry system implementation on 20 different criteria of medication documentation—a before-and-after study
Authors: Jungreithmayr Viktoria , Meid Andreas D. ,   Implementation Team, Bittmann Janina , Fabian Markus , Klein Ulrike , Kugler Silvia , Löpprich Martin , Reinhard Oliver , Scholz Lucienne , Zeeh Birgit , Bitz Wolfgang , Bugaj Till , Kihm Lars , Kopf Stefan , Liemann Anja , Wagenlechner Petra , Zemva Johanna , Benkert Claudia , Merle Christian , Roman Sergej , Welte Stefan , Haefeli Walter E. , Seidling Hanna M.
Published: October 2021

Background

The medication process is complex and error-prone. To avoid medication errors, a medication order should fulfil certain criteria, such as good readability and comprehensiveness. In this context, a computerized physician order entry (CPOE) system can be helpful. This study aims to investigate the distinct effects on the quality of prescription documentation of a CPOE system implemented on general wards in a large tertiary care hospital.

Methods

In a retrospective analysis, the prescriptions of two groups of 160 patients each were evaluated, with data collected before and after the introduction of a CPOE system. According to nationally available recommendations on prescription documentation, it was assessed whether each prescription fulfilled the established 20 criteria for a safe, complete, and actionable prescription. The resulting fulfilment scores (prescription-Fscores) were compared between the pre-implementation and the post-implementation group and a multivariable analysis was performed to identify the effects of further covariates, i.e., the prescription category, the ward, and the number of concurrently prescribed drugs. Additionally, the fulfilment of the 20 criteria was assessed at an individual criterion-level (denoted criteria-Fscores).

Results

The overall mean prescription-Fscore increased from 57.4% ± 12.0% (n = 1850 prescriptions) before to 89.8% ± 7.2% (n = 1592 prescriptions) after the implementation (p < 0.001). At the level of individual criteria, criteria-Fscores significantly improved in most criteria (n = 14), with 6 criteria reaching a total score of 100% after CPOE implementation. Four criteria showed no statistically significant difference and in two criteria, criteria-Fscores deteriorated significantly. A multivariable analysis confirmed the large impact of the CPOE implementation on prescription-Fscores which was consistent when adjusting for the confounding potential of further covariates.

Conclusions

While the quality of prescription documentation generally increases with implementation of a CPOE system, certain criteria are difficult to fulfil even with the help of a CPOE system. This highlights the need to accompany a CPOE implementation with a thorough evaluation that can provide important information on possible improvements of the software, training needs of prescribers, or the necessity of modifying the underlying clinical processes.
Traditional knowledge of medicinal plants on Gau Island, Fiji: differences between sixteen villages with unique characteristics of cultural value
Authors: Miyamoto Kana , Ehara Hiroshi , Thaman Randolph , Veitayaki Joeli , Yoshida Takehito , Kobayashi Hikaru
Published: October 2021

Background

Traditional resource management (TRM) systems develop depending on local conditions, such as climate, culture, and environment. Most studies have focused on the TRM system itself, excluding the people who manage the system, and the relationship between the system and the people. The use of resources and people is intimately linked through the practice of TRM systems on Gau Island and this relationship needs to be understood to advance sustainable resource use.

Methods

A survey was conducted on the use of medicinal plants on Gau Island, Fiji. Interviews were conducted from September 2013 to January 2015 with knowledgeable members of each community. The types of plants, prescriptions, and health problems were documented, and social and ecological factors affecting the sustainability of TRM of medicinal plants used in each of the 16 villages were statistically analysed by linear regression analysis.

Results

A total of 58 medicinal plants used on a daily basis to treat 27 health problems were identified on Gau. Two medicinal plants, Botebotekoro (Ageratum conyzoides) and Totodro (Centella asiatica), were used in all districts to treat various health problems. There were contrasts between the villages in the medical lore and prescriptions, and villages often used different traditional treatments than others for the same ailment; therefore, the status and knowledge of medicinal plants have developed distinctly in each village. Geographical and social factors have been suggested as possible reasons for the differences in regional resource utilisation among villages. Statistical analysis of the relationship between the state of TRM and social and ecological factors suggest that community solidarity has a positive impact on the sustainable practice of TRM. This study showed that traditional practices simultaneously contribute to the conservation of the natural environment and the binding of communities.

Conclusions

The results highlight the importance of understanding how TRM systems can contribute to the conservation of the natural environment. Cultural activities are essential to raise community solidarity, which has led to the sustainable use of natural resources. This suggests that merely documenting the use of medicinal plants is not enough to ensure that the skills and knowledge are passed down to the next generation.