bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the safety and efficacy of Zhenwu decoction as adjuvant therapy for the treatment of heart failure with reduced ejection fraction
Authors: Han Yue , Huang Lanlin , Zhong Guofu , Chang Xiao , Zhu Qinghua , Xu Mujuan , Mingtai Chen , Men Ling , Wang Ling
Published: January 2022

Introduction:

Heart failure with reduced ejection fraction (HFrEF) demonstrates a substanital threat to global public health. Several Chinese studies have been conducted to date evaluating the clinical efficacy of Zhenwu decoction (ZWD) as a treatment for HFrEF. The present systematic review will be conducted to more comprehensively evaluate the impact of ZWD on HFrEF outcomes.

Methods:

For this systematic review, all randomized controlled trials (RCTs) reporting on the effectiveness of ZWD as a treatment for HFrEF published as of December 30, 2021 in the Embase, PubMed, Springer, Web of Science, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure, and the Wan-Fang databases will be identified without any language or publication restrictions. Two researchers will independently choose investigations, extract information, and gauge research quality. Primary outcomes of interest will include all-cause mortality and HF-associated mortality. Secondary outcomes will include the incidence of adverse events, ultrasonic cardiographic indices (including left ventricular ejection fraction and left ventricular mass index), New York Heart Association grade, N-terminal pro-b-type natriuretic peptide, B-type natriuretic peptide, and 6-minute walking distance. RevMan v 5.3 will be used to conduct meta-analyses where possible, with descriptive or subgroup analyses otherwise being conducted. Data will be given as risk ratios for categorical variables and mean difference for continuous variables.

Results:

This comprehensive protocol will aid in the systematic and objective evaluation of the efficacy and safety of ZWD as a treatment for HFrEF, providing a scientific basis for the clinical utilization of ZWD.
Radiologic assessment of rupture risk in small (<5 mm) posterior communicating artery aneurysms
Authors: Kim Jang Hun , Choi Jong-Il , Lim Dong-Jun
Published: January 2022

Although previous studies have investigated the predictors of posterior communicating artery (PCoA) aneurysm rupture with clinical and radiologic parameters, the accessibility of “small PCoA aneurysms (<5 mm)” has rarely been reported. Here, we designed a study to identify the factors which are thought to be risky and prone to rupture in small PCoA aneurysms (<5 mm).

A total of 114 patients diagnosed with PCoA aneurysm under 5 mm in size on digital subtraction angiography were retrospectively enrolled and divided into ruptured (n = 51) and unruptured (n = 63) groups. Clinical variables were reviewed, and 10 radiologic parameters were obtained, including maximum diameter, height, width, neck width, aspect ratio, dome-to-neck ratio, bleb formation, size ratio, presence of fetal-type PCoA, and inflow angle. Statistical analyses were conducted to compare the groups (ruptured vs unruptured) and identify the risk factors for rupture.

High rupture rate of small PCoA aneurysm is noted (51/114, 44.7%). In the comparison analysis, parameters of size ratio (P = .045), aspect ratio (P = .001), and bleb formation (P = .015) were significantly different between the 2 groups. In the regression model, the aspect ratio (P = .045) and bleb formation (P = .004) were significantly associated with the rupture of aneurysm.

In respect of small (<5 mm) PCoA aneurysms of our cohort, morphologic parameters of “bleb formation” and “a high aspect ratio” are present more often in ruptured aneurysms as compared to unruptured aneurysms.
Modified procedure of anterior orbital exenteration enables eye socket reconstruction
Authors: Ma Ruiqi , Li Xiaofeng , Gan Lu , Guo Jie , Qian Jiang
Published: January 2022

The conventional procedure of anterior orbital exenteration is unfavorable for eye socket reconstruction, whereas a modified procedure enables socket reconstruction and prosthesis fitting. Our study aims to compare the cosmetic outcomes between these 2 surgical techniques.

We retrospectively recruited patients treated with modified or conventional exenteration during January 2015 to May 2021 in our hospital. The conventional approach was performed along with dermis-fat graft transplantation. The modified approach was conducted followed by eye socket reconstruction and eyelid blepharoplasty. The clinical data were collected and analyzed, including demographics, tumor characteristics, postoperative complications, tumor-related events, and cosmetic outcomes.

Forty-nine patients were consecutively recruited in this study, including 22 cases of modified exenteration and 27 cases of conventional exenteration. Forty-four subjects (89.8%) were diagnosed with ocular surface malignancies (conjunctival melanoma and squamous cell carcinoma) and 5 subjects (10.2%) were diagnosed with extraocular stage of uveal melanoma. After follow-up for 31.8 ± 17.1 months, the 1-, 2-, 5-year overall survival rate was calculated as 100%, 79.2%, and 59.2% in the Modified group, and 94.2%, 73.8%, and 51.5% in the Conventional group. Comparison of the survival curves showed no significant differences. In the Modified group, all patients received orbital implant placement and eye socket reconstruction. The implant motility was satisfactory in 12 cases (54.5%) with movements in 3 to 4 directions. The eyelid function was acceptable in 17 cases (77.3%) with no entropion, ectropion or lower lid laxity. Ocular prosthesis was delivered in 17 cases (77.3%) with successful fitting in 11 cases (64.7%). The self-rated cosmetic score was statistically (t test, P < .0001) higher in the Modified group (6.7 ± 0.9) than the Conventional group (2.2 ± 0.4).

The modified approach to anterior orbital exenteration enables eye socket reconstruction and cosmetic rehabilitation while still preserves the curable chance for the treatment of advanced periocular/intraocular malignancies.
Successful treatment of angioinvasive aspergillosis causing diaphragmatic rupture with bowel perforation and cerebral aspergillosis in a patient with FLT3-mutated acute myeloid leukemia
Authors: Bae Nan Young , Byun Ja Min , Kang Chang Kyung , Choe Pyoeng Gyun , Kim Nam Joong , Kim Min-Sung , Park Kyu Joo , Yoon Sung-Soo
Published: January 2022

Rationale:

Throughout the clinical course of acute myeloid leukemia (AML), aspergillosis infection remains a significant determinant of treatment outcomes and survival. To emphasize the importance of early diagnosis and appropriate application of integrated therapeutic approaches, we present a case of AML patient who survived through angioinvasive aspergillosis infection causing diaphragmatic rupture with bowel perforation and cerebral aspergillosis during active AML treatment.

Patient concerns:

A 39-year old male with FLT3-mutated AML was transferred to our hospital due to persistent fever after induction therapy.

Diagnosis and interventions:

During voriconazole treatment for his invasive pulmonary aspergillosis, the patient was diagnosed with colon perforation at splenic flexure and suspected perforation of left diaphragm with communication with left pleural space. Although pancytopenic, emergency laparotomy was performed with granulocyte transfusion. Also, dual antifungal therapy with voriconazole and micafungin was applied. With supportive care, he was able to successfully complete 3 cycles of consolidation using tyrosine kinase inhibitor. However, 80 days after the last chemotherapy, the patient experienced seizure caused by a single 1.5 cm sized enhancing mass in the right occipital lobe. Diagnostic and therapeutic mass removal was carried out, and pathology-confirmed cerebral aspergillosis was diagnosed.

Outcomes:

The patient's neurologic symptoms are resolved and he is leukemia free, but remains on voriconazole for his cerebral aspergillosis till this day.

Conclusions:

Our case highlights the importance of timely integrated intervention and adequate underlying disease control in treatment of invasive aspergillosis in immunocompromised patients. Such rigorous efforts can save even the most seemingly dismal case.
Case report of a delayed iatrogenic Pipkin type III femoral head fracture-dislocation
Authors: Li Qin-Wen , Zhou Cai-Sheng , Li Yu-Peng
Published: January 2022

Rationale

Pipkin III femoral head fracture dislocation (FHFD) is rarely observed in clinical practice, and its outcome is alarming. A considerable proportion of Pipkin III fractures result from repeated or forceful closed reduction of an irreducible FHFD. Pipkin type III fractures pose a therapeutic challenge. Most patients underwent total hip arthroplasty.

Patient concerns

A 34-year-old man experienced high-energy trauma to the left hip from a terrible traffic accident. Radiography and computed tomography (CT) at the local hospital revealed a left posterior FHFD. Emergency close reduction of the hip was performed.48 hours later, the patient was transferred to our institution. New radiography and CT examinations demonstrated an iatrogenic femoral neck fracture (FNF) associated with FHFD. In addition, a right talar fracture was observed.

Diagnosis

Pipkin III fracture combined with contralateral talar fracture.

Interventions

Considering his Pipkin fracture classification (Pipkin Type-III) and the time to surgery after his injury (>48 hours), the patient underwent left total hip arthroplasty uneventfully, followed by below-ankle plaster cast immobilization for his right ankle.

Outcomes

At the 6-month follow-up, the patient was able to walk pain-free, and plain radiographs were satisfactory, with no evidence of heterotopic ossification or osteonecrosis of the talus.

Lessons

Before emergency closed reduction, early recognition of the unique characteristics of an irreducible FHFD is essential to avoid iatrogenic femoral neck fracture.
Thromboelastography and Its Use in Pediatric Trauma Patients
Authors: Tanner Thomas E. , Drapkin Zachary , Fino Nora , Russell Katie , Chaulk David , Hewes Hilary A.
Published: January 2022

Background/Purpose

Thromboelastography's (TEG's) use in pediatric trauma patients is not widely studied. Identifying clotting cascade defects can direct decision making regarding blood product transfusion.

Methods

We performed a single-center retrospective review of all level 1 pediatric trauma patients. Data collected included demographics, diagnoses, Injury Severity Score, intensive care unit length of stay (ICU LOS), mortality, TEG values, and blood products received. We identified TEG values associated with mortality, ICU LOS, and need for blood product transfusion.

Results

A total of 237 trauma 1 patients were identified. After exclusions, 148 patients were included for analysis. Most patients were below TEG transfusion cut points. Patients with elevated reaction time, K value, and fibrinolysis at 30 minutes had increased odds of mortality with odds ratios of 1.71 (95% confidence interval [CI], 1.22–2.40), 1.94 (95% CI, 1.23–3.05), and 1.15 (95% CI, 1.03–1.28), respectively. For ICU LOS, elevated reaction time, K value, and fibrinolysis at 30 minutes, α angle, and maximum amplitude demonstrated hazard ratios of 0.76 (95% CI, 0.65–0.88), 0.82 (95% CI, 0.64–1.0), 0.95 (95% CI, 0.88–0.99), 1.05 (95% CI, 1.02–1.08), and 1.04 (95% CI, 1.01–1.06), respectively. There was no association between TEG and blood product transfusion.

Conclusions

Coagulopathic patients based on TEG had higher mortality. All TEG values, as they moved toward transfusion-trigger cut points, were associated with increased mortality.
Neoehrlichiosis
Authors: Jauregui Jean , Maniago Eric
Published: January 2022

Candidatus Neoehrlichia mikurensis is a gram-negative bacterium carried and spread by Ixodes ricinus ticks often found in Europe and Asia. It causes a disease process called neoehrlichiosis, which can result in vasculitis and thromboembolic events. This pathogen does not grow in typical culture medium, and most laboratories do not carry the specific polymerase chain reaction (PCR) test needed to detect neoehrlichiosis. If a patient presents to an emergency department complaining of a recent tick bite and symptoms of a deep vein thrombosis or pulmonary embolism, consider that these symptoms may be related. Treat the tick bite with doxycycline for 3 weeks and manage the thromboembolic event according to standard treatment of care.
Emergency Department Nursing Burnout and Resilience
Authors: Phillips Kate , Knowlton Mary , Riseden Jennifer
Published: January 2022

Burnout is a significant problem in emergency nursing, and it is associated with higher turnover rates than other disciplines of health care. Emergency nurses are highly susceptible to burnout due to continual exposure to traumatic events, varying work schedules, violence directed at staff, and, in recent times, due to the stressors of the COVID-19 pandemic. This literature review will (1) expose the causes of emergency department (ED) nurse burnout and (2) discuss strategies to build resilience in ED nurses. A systematic review of studies published in academic journals discussing burnout and resilience, specifically related to ED nurses, published in English between 2015 and 2019. The databases MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Education Source, Health Source: Nursing/Academic Edition, APA PsycArticles, Military and Government Collection, Gender Studies Database, SocINDEX, and PsycINFO were searched. Sixteen studies were included in this review. Work schedules and shift work, violence toward staff, and lack of management support were factors linked to burnout. Self-discipline, optimism, and goal-oriented behaviors evolved as characteristics of resilient ED nurses. Burnout rates among ED nurses are steep. Shift work, traumatic events, violence, and management support are determinants of burnout. Specialized actions can combat burnout and increase resilience. Nursing management can provide specific education to nurses to assist in this effort.
Presentation, Management, and Prevention of Herpes Zoster
Authors: Kaikai Samantha Michelle , Dowling Evans Dian
Published: January 2022

The purpose of the Research to Practice column is to review and critique current research articles that directly affect the advanced practice nurse's (APN's) practice in the emergency department. This review examines the findings of Schmidt and Rowbotham's (2017) article, “Aggressive Noninvasive Treatment of Acute Herpes Zoster for the Prevention of Postherpetic Neuralgia. Herpes Zoster: Postherpetic Neuralgia and Other Complications.” The authors completed an extensive literature review and created 6 key clinical recommendations for treating acute herpes zoster to prevent postherpetic neuralgia, including prevention, patient education and counseling, proper diagnosing, medication selection, and treatment specific to acute herpes zoster postherpetic neuralgia. This review provides a strategy to allow APNs to confidently recognize and treat acute herpes zoster and postherpetic neuralgia to reduce patient risks and avoid mistreatment of acute herpes zoster and postherpetic pain.
Meditation practice, mindfulness and pain-related outcomes in mindfulness-based treatment for episodic migraine
Authors: Hunt Carly , Letzen Janelle , Krimmel Samuel R , Burrowes Shana A.B. , Haythornthwaite Jennifer A. , Keaser Michael , Reid Matthew , Finan Patrick , Seminowicz David A.
Published: January 2022

Objectives

Mindfulness-based interventions (MBIs) have emerged as promising prophylactic episodic migraine treatments. The present study investigated biopsychosocial predictors and outcomes associated with formal, daily-life meditation practice in migraine patients undergoing MBI, and whether augmented mindfulness mechanistically underlies change.

Methods

Secondary analyses of clinical trial comparing data 12-week mindfulness-based stress reduction (MBSR+; n = 50) to stress management for headache (SMH; n = 48) were conducted.

Results

Pre-treatment mesocorticolimbic system functioning (i.e., greater resting state ventromedial prefrontal cortex-right nucleus accumbens [vmPFC-rNAC] functional connectivity) positively predicted meditation practice duration over MBSR+ (r = .58, p = .001), and moderated change in headache frequency from pre to post-treatment (b = -12.60, p = .02) such that patients with greater vmPFC-rNAC connectivity showed greater reductions in headache frequency. Patients who meditated more showed greater increases in mindfulness (b = .52, p = .02) and reductions in the helplessness facet of pain catastrophizing (b = -.13, p = .01), but not headache frequency, severity or impact. Augmented mindfulness mediated reductions in headache impact resulting from MBSR+, but not headache frequency.

Conclusions

Mesocorticolimbic system function is implicated in motivated behavior, and thus could be a target of augmentative interventions designed to enhance meditation practice engagement. Meditation practice appears to benefit pain-related cognitions, but not clinical pain, while mindfulness emerges as a mechanism of MBIs on headache impact, but not frequency. Further research is needed to investigate the day-to-day effects of meditation practice on pain, and continue to characterize the specific mechanisms of MBIs on headache outcomes.
SARS-CoV-2 seroprevalence in children, parents and school personnel from June 2020 to April 2021: cohort study of 55 schools in Switzerland
Authors: Ulyte Agne , Haile Sarah R. , Blankenberger Jacob , Radtke Thomas , Puhan Milo A. , Kriemler Susi
Published: January 2022

We measured SARS-CoV-2 seroprevalence in cohorts of children, parents and school personnel in 55 randomly selected schools in the canton of Zurich, Switzerland. In June-September 2020, seroprevalence was low (4.4% to 5.8%) in all cohorts. In March-April 2021, seroprevalence in children and parents (18.1% and 20.9%) was slightly higher than in school personnel (16.9%). Children’s seroprevalence was slightly higher in classes with infected main teachers and families with one infected parent, and substantially higher in families with two infected parents.
Positive attribute framing increases COVID-19 booster vaccine intention for unfamiliar vaccines
Authors: Barnes K. , Colagiuri B.
Published: January 2022

Positive framing has been proposed as a potential intervention to increase COVID-19 vaccination intentions. However, most available research has examined fictitious or unfamiliar treatments. This pre-registered study compared positively and negatively attribute-framed side effect information for real COVID-19 booster vaccines (AstraZeneca, Pfizer, Moderna) and measured booster intentions pre- and post-intervention in 1,222 UK-based participants. As hypothesised, vaccine familiarity significantly modulated the effect of framing. While positive framing was effective for the least familiar vaccine (i.e., Moderna), standard negative framing appeared to increase intentions for familiar vaccines (AstraZeneca/Pfizer), particularly among those with low baseline intentions. These findings provide important new evidence that positive framing could improve vaccine uptake globally when switches or new developments require individuals to receive less familiar vaccines – as is currently the case for millions of booster vaccines across the world. Positive framing of familiar vaccines, however, should be treated with caution.
Rapid deep widefield neuron finder driven by virtual calcium imaging data
Authors: Zhang Yuanlong , Zhang Guoxun , Han Xiaofei , Wu Jiamin , Li Ziwei , Li Xinyang , Xiao Guihua , Xie Hao , Fang Lu , Dai Qionghai
Published: January 2022

Widefield microscope provides optical access to multi-millimeter fields of view and thousands of neurons in mammalian brains at video rate. However, calcium imaging at cellular resolution has been mostly contaminated by tissue scattering and background signals, making neuronal activities extraction challenging and time-consuming. Here we present a deep widefield neuron finder (DeepWonder), which is fueled by simulated calcium recordings but effectively works on experimental data with an order of magnitude faster speed and improved inference accuracy than traditional approaches. The efficient DeepWonder accomplished fifty-fold signal-to-background ratio enhancement in processing terabytes-scale cortex-wide recording, with over 14000 neurons extracted in 17 hours in workstation-grade computing resources compared to nearly week-long processing time with previous methods. DeepWonder circumvented the numerous computational resources and could serve as a guideline to massive data processing in widefield neuronal imaging.
CD38 expression by antigen-specific CD4 T cells correlates with sputum bacterial load at time of tuberculosis diagnosis and is significantly restored 5-months after treatment initiation
Authors: Hiza Hellen , Hella Jerry , Arbués Ainhoa , Sasamalo Mohamed , Misana Veronica , Fellay Jacques , Gagneux Sébastien , Reither Klaus , Portevin Damien
Published: January 2022

T cell activation markers (TAM) expressed by antigen-specific T cells constitute promising candidates to attest the presence of an active infection by Mycobacterium tuberculosis (Mtb). Reciprocally, their modulation may be used to assess antibiotic treatment efficacy and eventually attest disease resolution. We hypothesized that the phenotype of Mtb-specific T cells may be quantitatively impacted by the load of bacteria present in a patient. We recruited 105 Tanzanian adult tuberculosis (TB) patients and obtained blood before and after 5 months of antibiotic treatment. We studied relationships between patients’ clinical characteristics of disease severity and microbiological as well as molecular proxies of bacterial load in sputum at the time of diagnosis. Besides, we measured by flow cytometry the expression of CD38 or CD27 on CD4+ T cells producing interferon gamma (IFN-γ) and/or tumor necrosis factor-alpha (TNF-α) in response to a synthetic peptide pool covering the sequences of Mtb antigens ESAT-6, CFP-10 and TB10.4. Reflecting the difficulty to extrapolate bacterial burden from a single end-point read-out, we observed statistically significant, but weak, correlations between Xpert MTB/RIF, MBLA and time to culture positivity. Unlike CD27, the resolution of CD38 expression by antigen-specific T cells was observed readily following 5 months of antibiotic therapy. In addition, only the intensity of CD38-TAM signals measured at diagnosis significantly correlated with Mtb 16S RNA recovered from patients’ sputa. Altogether, our data support CD38-TAM as an accurate marker of infection resolution and a sputum-independent proxy of bacterial load.
The impacts of increased global vaccine sharing on the COVID-19 pandemic; a retrospective modelling study
Authors: Moore Sam , Hill Edward M. , Dyson Louise , Tildesley Michael J. , Keeling Matt J.
Published: January 2022

Background

The SARS-CoV-2 pandemic has generated considerable morbidity and mortality world-wide. While the protection offered by vaccines (and booster doses) offers a method of mitigating the worst effects, by the end of 2021 the distribution of vaccine was highly heterogeneous with some countries achieving over 90% coverage in adults by the end of 2021, while others have less than 2%. In part, this is due to the availability of sufficient vaccine, although vaccine hesitancy also plays a role.

Methods

We use an age-structured model of SARS-CoV-2 dynamics, matched to national data from 152 countries, to investigate the global impact of different vaccine sharing protocols during 2021. We assume a direct relationship between the emergence of variants with increased transmissibility and the cumulative amount of global infection, such that lower global prevalence leads to a lower reproductive number within each country. We compare five vaccine sharing scenarios, from the current situation, through sharing once a particular within-country threshold is reached (e.g. all over 40s have received 2 doses), to full sharing where all countries achieve equal age-dependent vaccine deployment.

Findings

Compared to the observed distribution of vaccine uptake, we estimate full vaccine sharing would have generated a 1.5% (PI -0.1 - 4.5%) reduction in infections and a 11.3% (PI 0.6 - 23.2%) reduction in mortality globally by January 2022. The greatest benefit of vaccine sharing would have been experienced by low and middle income countries, who see an average 5.2% (PI 2.5% - 10.4%) infection reduction and 26.8% (PI 24.1% - 31.3%) mortality reduction. Many high income countries, that have had high vaccine uptake (most notably Canada, Chile, UK and USA), suffer increased infections and mortality under most of the sharing protocols investigated, assuming no other counter measures had been taken. However, if reductions in vaccine supply in these countries had been offset by prolonged use of non-pharmaceutical intervention measures, we predict far greater reductions in global infection and mortality of 64.5% (PI 62.6% - 65.4%) and 62.8% (PI 44.0% - 76.3%), respectively.

Interpretation

By itself, our results suggest that although more equitable vaccine distribution would have had limited impact on overall infection numbers, vaccine sharing would have substantially reduced global mortality by providing earlier protection of the most vulnerable. If increased vaccine sharing from high income nations had been combined with slower easing of non pharmaceutical interventions to compensate for this, a large reduction in both infection and mortality globally would be expected, confounded by a lower risk of new variants arising.
Local PI(4,5)P2 generation controls fusion pore expansion during exocytosis
Authors: Omar-Hmeadi Muhmmad , Guček Alenka , Barg Sebastian
Published: January 2022

Phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) is an important signaling phospholipid that is required for regulated exocytosis and some forms of endocytosis. The two processes share a topologically similar pore structure that connects the vesicle lumen with the outside. Widening of the fusion pore during exocytosis leads to cargo release, while its closure initiates kiss&run or cavicapture endocytosis. We show here, using live cell TIRF microscopy of insulin granule exocytosis, that transient accumulation of PI(4,5)P2 at the release site recruits components of the endocytic fission machinery, and stalls the late fusion pore expansion that is required for peptide release. The absence of clathrin differentiates this mechanism from clathrin-mediated endocytosis. The PI(4,5)P2 transients result from local phosphatidylinositol-phosphate-5-kinase-1c (PIP5K1c) activity, and knockdown of PIP5K1c, or optogenetic ablation of PI(4,5)P2 promotes fusion pore expansion. Thus, local phospholipid signaling controls fusion pore expansion peptide release through an unconventional endocytic mechanism.
The thresholding problem and variability in the EEG graph network parameters
Authors: Adamovich Timofey , Zakharov Ilya , Tabueva Anna , Malykh Sergey
Published: January 2022

Graph thresholding is a frequently used practice of eliminating the weak connections in brain functional connectivity graphs. The main aim of the procedure is to delete the spurious connections in the data. However, the choice of the threshold is arbitrary, and the effect of the threshold choice is not fully understood. Here we present the description of the changes in the global measures of a functional connectivity graph depending on the different proportional thresholds based on the 146 resting-state EEG recordings. The dynamics is presented in five different synchronization measures (wPLI, ImCoh, Coherence, ciPLV, PPC) in sensors and source spaces. The analysis shows significant changes in the graph’s global connectivity measures as a function of the chosen threshold which may influence the outcome of the study. The choice of the threshold could lead to different study conclusions; thus it is necessary to improve the reasoning behind the choice of the different analytic options and consider the adoption of different analytic approaches. We also proposed some ways of improving the procedure of thresholding in functional connectivity research.
Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine
Authors: Li Dapeng , Martinez David R. , Schäfer Alexandra , Chen Haiyan , Barr Maggie , Sutherland Laura L. , Lee Esther , Parks Robert , Mielke Dieter , Edwards Whitney , Newman Amanda , Bock Kevin W. , Minai Mahnaz , Nagata Bianca M. , Gagne Matthew , Douek Daniel C. , DeMarco C. Todd , Denny Thomas N. , Oguin Thomas H. , Brown Alecia , Rountree Wes , Wang Yunfei , Mansouri Katayoun , Edwards Robert J. , Ferrari Guido , Sempowski Gregory D. , Eaton Amanda , Tang Juanjie , Cain Derek W. , Santra Sampa , Pardi Norbert , Weissman Drew , Tomai Mark A. , Fox Christopher B. , Moore Ian N. , Andersen Hanne , Lewis Mark G. , Golding Hana , Seder Robert , Khurana Surender , Baric Ralph S. , Montefiori David C. , Saunders Kevin O. , Haynes Barton F.
Published: January 2022

Coronavirus vaccines that are highly effective against SARS-CoV-2 variants are needed to control the current pandemic. We previously reported a receptor-binding domain (RBD) sortase A-conjugated ferritin nanoparticle (RBD-scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected monkeys from SARS-CoV-2 WA-1 infection. Here, we demonstrate SARS-CoV-2 RBD-scNP immunization induces potent neutralizing antibodies in non-human primates (NHPs) against all eight SARS-CoV-2 variants tested including the Beta, Delta, and Omicron variants. The Omicron variant was neutralized by RBD-scNP-induced serum antibodies with a mean of 10.6-fold reduction of ID50 titers compared to SARS-CoV-2 D614G. Immunization with RBD-scNPs protected NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protected mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect NHPs and mice from multiple different SARS-related viruses. Such a vaccine could provide the needed immunity to slow the spread of and reduce disease caused by SARS-CoV-2 variants such as Delta and Omicron.
Transcriptomic and phenomic investigations reveal elements in biofilm repression and formation in the cyanobacteriumSynechococcus elongatusPCC 7942
Authors: Simkovsky Ryan , Parnasa Rami , Wang Jingtong , Nagar Elad , Zecharia Eli , Suban Shiran , Yegorov Yevgeni , Veltman Boris , Sendersky Eleonora , Schwarz Rakefet , Golden Susan S.
Published: January 2022

Biofilm formation by photosynthetic organisms is a complex behavior that serves multiple functions in the environment. Biofilm formation in the unicellular cyanobacteriumSynechococcus elongatusPCC 7942 is regulated in part by a set of small secreted proteins that promotes biofilm formation and a self-suppression mechanism that prevents their expression. Little is known about the regulatory and structural components of the biofilms in PCC 7942, or response to the suppressor signal(s). We performed transcriptomics (RNA-Seq) and phenomics (RB-TnSeq) screens that identified four genes involved in biofilm formation and regulation, more than 25 additional candidates that may impact biofilm formation, and revealed the transcriptomic adaptation to the biofilm state. In so doing, we compared the effectiveness of these two approaches for gene discovery.
Evaluation of heat inactivation of human norovirus in freshwater clams using human intestinal enteroids
Authors: Hayashi Tsuyoshi , Yamaoka Yoko , Ito Atsushi , Kamaishi Takashi , Estes Mary K. , Muramatsu Masamichi , Murakami Kosuke
Published: January 2022

Foodborne disease attributed to consumption of shellfish contaminated with human norovirus (HuNoV) is one of many global health concerns. Our study aimed to determine conditions of heat-inactivation of HuNoV in freshwater clams (Corbicula japonica) using a recently developed HuNoV cultivation system employing stem-cell derived human intestinal enteroids (HIEs). We first measured the internal temperature of clam tissue in a water bath during boiling at 90 °C and found that approximately 2 minutes are required for the tissue to reach 90 °C. Next, GII.4 HuNoV was spiked into the center of the clam tissue followed by boiling at 90 °C for 1, 2, 3, or 4 minutes. The infectivity of the HuNoV in clam tissue homogenates was evaluated using HIEs. We demonstrated that HuNoV in unboiled clam tissue homogenates replicated in HIEs, whereas infectivity was lost in all boiled samples, indicating that heat treatment at 90 °C for 1 minute is sufficient to inactivate HuNoV in freshwater clams. To our knowledge, this is the first study to determine the infectivity of HuNoV tolerability in shellfish using HIEs and our results will be informative to develop strategies to inactivate HuNoV in foods.
Inducible degradation of dosage compensation protein DPY-27 facilitates isolation of Caenorhabditis elegans males for molecular and biochemical analyses
Authors: Li Qianyan , Kaur Arshdeep , Mallory Benjamin , Hariri Sara , Engebrecht JoAnne
Published: January 2022

Biological sex affects numerous aspects of biology, yet how sex influences different biological processes has not been extensively studied at the molecular level. Caenorhabditis elegans, with both hermaphrodites (functionally females as adults) and males, is an excellent system to uncover how sex influences physiology. Here, we describe a method to isolate large quantities of C. elegans males by conditionally degrading DPY-27, a component of the dosage compensation complex essential for hermaphrodite, but not male, development. We show that germ cells from males isolated following DPY-27 degradation undergo meiosis and spermiogenesis like wild type and are competent to mate and produce viable offspring. We demonstrate the efficacy of this system by analyzing gene expression and performing affinity pull-downs from male worm extracts.
Shared and distinct functional effects of patient-specific Tbr1 mutations on cortical development
Authors: Co Marissa , Barnard Rebecca A. , Jahncke Jennifer N. , Grindstaff Sally , Fedorov Lev M. , Adey Andrew C. , Wright Kevin M. , O’Roak Brian J.
Published: January 2022

Predicted loss-of-function and missense heterozygous de novo mutations of TBR1 are strongly associated with intellectual disability and autism. The functional effects of these heterogeneous mutations on cortical development and genotype-phenotype relationships have yet to be explored. We characterized mouse models carrying patient mutations A136PfsX80 and K228E, finding convergent and discordant phenotypes. The A136PfsX80 mutation is loss-of-function and allelic to the Tbr1 knockout. In contrast, K228E causes significant upregulation of TBR1. Heterozygosity of either mutation produces axon defects, including reduction of the anterior commissure, and CTIP2 downregulation in adult cortex. While mice lacking TBR1 show extensive cortical apoptosis and inverted layering, K228E homozygotes show normal apoptosis levels and a complex layering phenotype—suggesting partial, yet abnormal, function of the allele. The construct and face validity of these Tbr1 patient mutation mice suggests they will be valuable translational models for studying the function of this essential brain transcription factor.
Gnas ablation in CD11c+ cells prevents high-fat diet-induced obesity by elevating adipose tissue catecholamine levels and thermogenesis
Authors: Zeng Liping , Herdman D. Scott , Lee Jihyung , Tao Ailin , Das Manasi , Bertin Samuel , Eckmann Lars , Mahata Sushil , Devulapalli Shwetha , Patel Hemal H. , Molina Anthony J.A. , Osborn Olivia , Corr Maripat , Raz Eyal , Webster Nicholas J.G.
Published: January 2022

CD11c+ immune cells are a potential therapeutic target for treatment of obesity-related insulin resistance and type 2 diabetes (T2D). In obesity, CD11c+ immune cells are recruited to white adipose tissue and create an inflammatory state that causes both insulin and catecholamine resistance. In this study, we found that ablation of Gnas, the gene that encodes Gas, in CD11c expressing cells protects mice from high-fat diet-induced obesity, glucose intolerance and insulin resistance. GnasΔCD11c mice (KO) had increased oxygen consumption, energy expenditure, and beigeing of white adipose tissue (WAT). Transplantation studies showed that the lean phenotype was conferred by bone marrow-derived cells and the absence of T and B cells by crossing the KO to a Rag1-/- background did not alter the phenotype. Notably, we observed elevated norepinephrine and elevated cAMP signaling in the WAT of KO mice. The KO adipose tissue also had reduced expression of catecholamine transport and degradation enzymes. Collectively, our results identified an important role of Gas in CD11c+ cells in whole body metabolism regulation by controlling norepinephrine levels in WAT, modulating catecholamine-induced lipolysis and increasing thermogenesis that together created a lean phenotype.
Fe(III)-dependent anaerobic methane-oxidizing activity in a deep underground borehole demonstrated by in-situ pressure groundwater incubation
Authors: Nishimura Hiroki , Kouduka Mariko , Fukuda Akari , Ishimura Toyoho , Amano Yuki , Beppu Hikari , Miyakawa Kazuya , Suzuki Yohey
Published: January 2022

The family Methanoperedenaceae archaea mediate anaerobic oxidation of methane (AOM) in various terrestrial environments. In this study, we newly developed a high-pressure laboratory incubation system by controlling hydraulic pressure ranging from ambient to 5 MPa. Using the system, we investigated groundwater from 214- and 249-m deep boreholes at Horonobe Underground Research Laboratory, Japan, where the high and low abundances of Methanoperedenaceae archaea have been revealed by genome-resolved metagenomics, respectively. We incubated the groundwater samples amended with or without amorphous Fe(III) as an electron acceptor and 13C-labelled methane at an in-situ pressure of 1.6 MPa. After three to seven-day incubation, AOM activities were not detected from the 249-m deep groundwater but from the 214-m deep groundwater. The AOM rates were 93.7 ± 40.6 and 27.7 ± 37.5 nM/day with and without Fe(III) amendment. To clarify the differences in AOM activity between the 214- and 249-m deep groundwater samples, we characterized Fe(III) contents in suspended particulates collected by filtration. The particulates were not visible in the 249-m deep groundwater on the filter, while they were abundant and contained Fe(III)-bearing phyllosilicates in the 214-m deep groundwater. These results support the in-situ activity of Fe(III)-dependent AOM in the deep subsurface borehole.
What stabilizes pre-folded structures in the intrinsically disordered α-helical binding motifs?
Authors: Hadži San , Purič Samo , Zavrtanik Uroš , Vranken Wim
Published: January 2022

Many examples are known of regions of intrinsically disordered proteins (IDPs) that fold into α-helices upon binding their globular protein targets. In their unbound state these regions possess a small amount of residual helicity, referred to as pre-folded structure, which has been studied on case by case basis. In order to investigate what determines these pre-folded structures we compiled a database of peptides that fold-upon-binding, and experimentally characterized their helicity in the unbound and target-bound state. These regions are more hydrophobic and lack proline residues compared to IDPs in general. On average they possess about 17% helicity in the pre-folded state and gain 40% of helicity upon target binding. We observe that the locations of pre-folded helical regions strongly overlap with those in the targetbound IDPs. To understand this correlation, we analyzed per-residue energetic contributions stabilizing helical structure and found that target-interacting IDP have higher helix propensity. Notably, leucine is the most common residue involved in IDP-target interactions and, due to its high helix propensity, it strongly stabilizes pre-folded helical structures. For many IDP binding motifs, particularly those enriched in leucine, we observe that they not only mediate target-interactions but also confer stability to the pre-folded structure. Collectively, this shows that the formation of pre-folded helical elements is coupled to the IDP-target interactions, explaining why such elements are a common feature of α-helical binding motifs. Moreover, it probably explains the preference for leucine among IDP-target hotspots, even though this residue is underrepresented among hotspots in the interfaces between globular proteins.
5-Amino-1H-benzimidazole-2(3H)-thione: molecular, crystal structure and Hirshfeld surface analysis
Authors: Rakhmonova Dilnoza , Gapurova Lobar , Razzoqova Surayyo , Kadirova Shakhnoza , Torambetov Batirbay , Kadirova Zukhra , Shishkina Svitlana
Published: January 2022

The title compound, C7H7N3S, which has potential biological activity, can be used as a ligand in metal complexation. This compound exists as the thione tautomer in the crystal phase, which is confirmed by the study of its molecular structure. The amino group has pyramidal configuration. In the crystal phase, the two independent molecules in the asymmetric unit form tetramers as a result of N—H...S hydrogen bonds. These tetramers are linked by N—H...N hydrogen bonds, forming chains/tubes in the [010] direction. The Hirshfeld surface analysis showed that the highest contribution to the total surface is provided by H...H interactions as well as S...H/H...S and C...H/H...C contacts associated with X—H...S hydrogen bonds and X—H...C(π) interactions.
β-D-Galactopyranosyl-(1→4)–2-amino-2-deoxy-α-D-glucopyranose hydrochloride monohydrate (lactosamine)
Authors: Mossine Valeri V. , Kelley Steven P. , Mawhinney Thomas P.
Published: January 2022

The title compound, C12H24NO10
+·Cl−·H2O, (I), crystallizes in the monoclinic space group P21 and exists as a monohydrate of a monosubstituted ammonium chloride salt, with the reducing carbohydrate portion existing exclusively as the α-pyranose tautomer. The glycosidic bond geometry in (I) is stabilized by an intramolecular hydrogen bond and is close to that found in crystalline α-lactose. All heteroatoms except glucopyranose ring O4 participate in an extensive hydrogen-bonding network, which propagates in all directions in the crystal structure of (I).
Chief marketing officers' future focus and firms' sustainability marketing commitment
Authors: Thu Nguyen NQ , Tho Nguyen Dinh
Published: January 2022

Purpose

This study examines a moderated moderation model in which the hardiness of chief marketing officers (CMOs) moderates the relationship between CMOs' future focus and firms' sustainability marketing commitment (SMC), and this moderating effect is moderated by CMOs' proactive personality.

Design/methodology/approach

A sample of 298 CMOs of firms in Vietnam was surveyed to collect data. Confirmatory factor analysis was employed to validate the measures of the constructs used in the model and structural equation modeling (SEM) was used to test the model and hypotheses.

Findings

The SEM results reveal that CMOs' future focus had a positive relationship with firms' SMC. Furthermore, both CMOs' hardiness and its interaction with CMOs' future focus had positive effects on firms' SMC. Finally, the three-way interaction between CMOs' future focus, hardiness and proactive personality had a positive effect on firms' SMC.

Practical implications

The study findings assist firms in emerging markets in understanding the roles of some key personality-based resources of CMOs in fostering firms' SMC.

Originality/value

This study is among the first to investigate the roles of CMOs' personality-based resources (i.e. future focus, hardiness and proactive personality) in firms' SMC, offering insight into the sustainability marketing literature.
Crisis communication, social media and natural disasters – the use of Twitter by local governments during the 2016 Italian earthquake
Authors: Splendiani Simone , Capriello Antonella
Published: January 2022

Purpose

The objective of this exploratory research is to investigate the role of Twitter in crisis communication by analysing all the earthquake-related messages from local public authorities in four Italian regions (Abruzzo, Lazio, Marche and Umbria) during the seismic sequence that began on 24th August 2016 and finished at the end of January 2017.

Design/methodology/approach

The study is based on a manual data collection of earthquake-related tweets. Founded on a theoretical framework, the data analysis has been developed both through textual analysis and in-depth interpretation by two researchers to catalogue the messages according to identified categories.

Findings

It emerges that the affected Italian regions used Twitter only for information coverage without offering a complete and detailed picture of the disaster. Most of the tweets concerned daily statements by politicians or regional administrators engaged in crisis management, while an accurate selection of the topics and messages to be launched does not emerge, with significant implications on the effectiveness of the tweeting activity itself.

Originality/value

This paper aims to contribute to the literature on crisis communication and social media during a natural disaster, highlighting the criticalities shown by the Italian case studies. The originality of this study relates to the comparative examination of Twitter activities for four regional government bodies involved in the 2016 Italian earthquake.
Quadri-directional optical bending sensor using side-emitting POF integrated with wearable device technology in smart glove
Authors: Lin Miao-Tzu
Published: January 2022

Purpose

It is important to monitor wrist four direction movements (flexion, extension, adduction and abduction) for hand healthcare, wrist rehabilitation and upper limb exercise, and so on. The purpose of this study is to develop a quadri-directional optical bending sensor that integrated wearable device technology in a smart glove to detect wrist four direction movements.

Design/methodology/approach

The quadri-directional optical bending sensor was designed with a microcontroller board, a Bluetooth wireless module, a side-emitting polymeric optical fibre (POF), an infrared light emitting diode and four phototransistors. A linear equation was deduced to calculate bending angle from detecting sensor value of Arduino microcontroller. The bending angle values could be seen by the smartphone screen, so the system has a good human–machine interface function.

Findings

The light emission by macro-bending of the side-emitting POFs that the transmittance of the outer side is greater than the inner. The bending POFs lateral emission phenomenon integrated with phototransistors on the edge is suitable for the development of bending sensors.

Originality/value

This study is to develop a novel quadri-directional optical bending sensor to replace two bi-direction sensors or four uni-direction sensors for wrist four direction movements monitoring.