bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Stenocarpella maydis and Stenocarpella macrospora Causing Diplodia Ear Rot in Kentucky
Authors: Anderson Nolan R. , Wise Kiersten A.
Published: August 2023

Kentucky corn ( Zea mays L.) fields were surveyed in 2019 and 2020 for the presence of Diplodia ear rot (DER) to document the prevalence and distribution of the disease and determine the frequency of DER causal agents Stenocarpella maydis (Berk.) Sutton and Stenocarpella macrospora (Earle) Sutton. In 2019, 92 fields were surveyed, and 125 of 4,600 inspected ears were confirmed to be infected by either causal agent. In 2020, 87 fields were surveyed, and 45 of 4,350 ears examined were confirmed to be infected by either causal agent. Fungi were isolated from corn ears with suspected signs and symptoms of DER, and the causal species was identified based on conidia morphology. S. macrospora was identified in 33.8% of inspected ears in 2019 and 36.9% in 2020, and S. maydis was confirmed in 66.2% of inspected ears in 2019 and 63.1% in 2020. In 2019, ears infected with S. macrospora had greater disease severity than those infected with S. maydis ( P = 0.0245). The incidence of DER was greater in fields with a previous crop rotation of double crop wheat/soybean ( P = 0.0113); however, DER severity was not affected by previous crop rotation ( P = 0.3454). The results from this study emphasize the importance of including both Stenocarpella species in future research and discussions on DER.
Implementation of Specialty Tobacco Use Disorder Services in a Community Health Setting: Support for Enhanced Prescription Practices
Authors: Meredith Lindsay R. , Hurley Brian , Friedman Theodore C. , Lee Martin L. , Rodriguez Luz , Lopez Briana , Mtume Norma , Dixon Tasha , Belani Hrishikesh K. , Hsieh Susan , Ray Lara A.
Published: August 2023

Objectives

Although public efforts to reduce tobacco use have been successful, millions of US adults currently smoke tobacco. Reducing the public health burden of tobacco use disorder (TUD) and eliminating disparities experienced by underresourced communities requires increased accessibility to services. The goal of this study was to assess whether prescriptions for evidence-based medications for tobacco treatment showed steeper growth rates among community health clinics providing specialty TUD services as compared with treatment as usual.

Methods

Clinic-wide data on prescriptions for smoking cessation pharmacotherapy at 18 primary care or mental health community clinics operated by Los Angeles County were retrieved for 4 years of an ongoing implementation trial. Specialty services included behavioral counseling and medications for tobacco treatment. Descriptive statistics characterized prescriptions rates across clinics and time. Analyses compared the slopes of the changes between intervention groups across time for primary care and mental health sites.

Results

Within primary care clinics, the most commonly prescribed smoking cessation medications were nicotine patches, nicotine gum, and varenicline. Throughout the trial, all clinics displayed increased rates of prescribing smoking cessation medications. Analytic results supported overall steeper increases in prescription rates for these medications among clinics randomized to specialty services versus treatment as usual within primary care (P= 0.020) and mental health sites (P= 0.004).

Conclusions

This work provides support for the effectiveness of community-based implementation interventions that promote prescribing smoking cessation medications with the potential to reduce health disparities among communities at greater risk for TUD and its consequences.
Vasa Previa
Authors: Oyelese Yinka , Javinani Ali , Shamshirsaz Alireza A.
Published: August 2023

Vasa previa refers to unprotected fetal vessels running through the membranes over the cervix. Until recently, this condition was associated with an exceedingly high perinatal mortality rate attributable to fetal exsanguination when the membranes ruptured. However, ultrasonography has made it possible to diagnose the condition prenatally, allowing cesarean delivery before labor or rupture of the membranes. Several recent studies have indicated excellent outcomes with prenatally diagnosed vasa previa. However, outcomes continue to be dismal when vasa previa is undiagnosed before labor. Risk factors for vasa previa include second-trimester placenta previa and low-lying placentas, velamentous cord insertion, placentas with accessory lobes, in vitro fertilization, and multifetal gestations. Recognition of individuals who are at risk and screening them will greatly decrease the mortality rate from this condition. Because of the relative rarity of vasa previa, there are no randomized controlled trials to guide management. Therefore, recommendations on the diagnosis and management of vasa previa are based largely on cohort studies and expert opinion. This Clinical Expert Series review addresses the epidemiology, pathophysiology, natural history, diagnosis and management of vasa previa, as well as innovative treatments for the condition.
The Effect of Reiki on Pain Applied to Patients With Cancer
Authors: Avci Abdullah , Gün Meral
Published: August 2023

Pain, the most common and major source of fear in patients with cancer, reduces the quality of life. This systematic review was conducted to determine the effect of Reiki on pain applied to patients with cancer. The creation of a systematic review protocol and the writing of the article were based on the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) criteria. The literature review was carried out in PubMed, Scopus, and Cochrane Library databases. Seven experimental and quasi-experimental studies met the inclusion criteria, and a total of 572 patients with cancer with sample sizes ranging from 18 to 180 were included. In-person Reiki was applied in 6 of the studies included in the systematic review, while in one of them, distance Reiki was applied. Although Reiki was found to reduce pain in 5 studies included in the review, it was determined that it was not effective on pain in 2 studies. A limited number of studies show that Reiki applied to patients with cancer has a positive effect on pain. It is recommended to conduct more randomized controlled trials with a high methodological quality that examine the effectiveness of Reiki application for patients with cancer.
Holistic Hypertension Management
Authors: Berry Rachel K. , Peck Jessica L.
Published: August 2023

Hypertension (HTN) is a major health care problem affecting nearly half of American's adult population. HTN is one of the costliest diagnoses among cardiovascular disease and leads to other major cardiovascular complications, which increase overall morbidity and mortality. Of those diagnosed with HTN in America, only one-fourth of patients are living with well-controlled HTN. This evidenced-based HTN management practice innovation was conducted to explore evidenced-based, holistic nursing practice of a low-sodium dietary approach to stop hypertension (DASH) diet, and exercise alongside antihypertensive medication management in decreasing systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adult patients diagnosed with HTN. This community-based holistic care initiative supports data previously published, which suggests a low-sodium DASH diet, exercise, and antihypertensive medication management are effective in decreasing SBP and DBP. This project supported clinicians seeking to integrate a complementary holistic and traditional approach to HTN management in patients diagnosed with HTN.
High Astigmatism Secondary to Peripheral Ectasia Recurrence in Postpenetrating Keratoplasty Eyes Managed With Miniscleral Contact Lenses
Authors: Law Elizabeth , Moledina Malik , Sexton Ian , Myerscough James
Published: August 2023

Objectives:

After penetrating keratoplasty (PK) for keratoconus, vision can be impaired by high-degree astigmatism, particularly in those patients with recurrent peripheral ectasia. Scleral contact lenses (CLs) have long been used in the management of keratoconus both in treatment-naive corneas and those postcorneal transplants. We report the use of miniscleral CLs and their related visual and clinical outcomes in a series of patients with post-PK peripheral rim ectasia.

Methods:

In this retrospective case series, 5 patients (7 eyes) presented because of reduced visual acuity with their spectacles/CLs and/or reduced comfort with their existing rigid gas-permeable lenses. All patients in this series underwent PK more than two decades ago for keratoconus (mean 28.7 years±7.2). All patients demonstrated characteristic thinning at the graft–host junction, with anterior chamber deepening. Central corneas had remained clear in all patients inferring high visual potential. Contact lenses used were No 7 Comfort 15 miniscleral and the Onefit MED scleral with 14.5 mm and 15.6 mm diameters, respectively.

Results:

All eyes achieved a best-corrected visual acuity of 6/9 or greater. One case had difficulty with insertion and removal and has since discontinued wearing lens at this time. All others are successfully wearing the lenses regularly.

Conclusion:

Despite advances in CL design, surgical management is still required in some patients. Miniscleral CLs are effective in the refractive management of peripheral ectasia in keratoconic post-PK eyes and should be considered in such eyes before proceeding with repeat surgical intervention.
Carbapenem Appropriateness in a Rural Facility
Authors: Cole Jennifer L.
Published: August 2023

Objective

Inappropriate carbapenem prescribing leads to increased resistance, secondary infections, serious side effects, and wasted resources. A history of penicillin allergy has been identified as a potential trigger for inappropriate carbapenem prescribing. The PEN-FAST score is a validated tool that provides a high negative predictive value for allergic reaction with low scores. The objectives of this study were to determine the proportion of imipenem/cilastatin and meropenem prescriptions deemed appropriate according to published criteria and to evaluate the proportion of penicillin allergies with a low PEN-FAST score.

Methods

A convenience sample of 100 carbapenem prescriptions (imipenem/cilastatin [n = 50] and meropenem [n = 50]) was evaluated with a retrospective chart review. Objective published criteria were used to assign a score of appropriate, suboptimal, or inappropriate. In patients with a history of penicillin allergy, a PEN-FAST score was retrospectively applied. Indications for use and risk factors for resistant infections were also recorded. Analysis was largely descriptive statistics, with a χ2 used to compare drug cohorts in R Studio.

Results

Prescribing was considered appropriate (25%), suboptimal (20%), and inappropriate (55%) in the combined cohort. Inappropriate prescribing was more common with imipenem/cilastatin (66% vs. 44%, P = 0.03). In 28 patients with a historical penicillin allergy, the PEN-FAST score was 0 (low risk for reaction) in the majority of cases (93%).

Conclusions

Inappropriate carbapenem prescribing is common at the study facility and may benefit from directed antimicrobial stewardship measures. Implementing the PEN-FAST scoring method may be beneficial in a multifaceted intervention.
Worksite Health Promotion and Work Performance
Authors: van der Put Anne C. , Mandemakers Jornt J. , de Wit John B.F. , van der Lippe Tanja
Published: August 2023

Objective

This work aimed to study whether being aware of the existence of worksite health promotion (WHP), using it, or both are related to employees' task and contextual performance.

Methods

Multilevel cross-sectional data came from the European Sustainable Workforce Survey, with data from more than 11,000 employees in 259 organizations. Generalized structural equation modeling was used to examine two types of WHP: healthy menus and sports facilities.

Results

Awareness of healthy menus and sports facilities was positively associated with task and contextual performance. Healthy menus use was related to both higher task and contextual performance, whereas sports facilities use was only associated with contextual performance. The relation of WHP use was stronger for contextual than for task performance.

Conclusions

Organizations should ensure that employees are aware of the availability of WHP as well as stimulate employees to make use of it.
Pancreatic cancer-related pain: mechanism and management
Authors: Wu Meijing , Zhu Afang , Shen Le
Published: August 2023

Pancreatic cancer-related pain (PCRP) gains widespread attention for its high prevalence, extreme complexity, poor prognosis, and decreased survival rate. Current treatment of PCRP remains unsatisfactory since the underlying mechanism is not clear. The occurrence of PCRP is mainly related to the neurotropic nature of pancreatic cancer, and perineural invasion, neural remodeling and plasticity play important roles. Upon the understanding of PCRP mechanism, the management of PCRP is a multidisciplinary and multifaceted strategy. Traditional pain medications, invasive or intervention treatment, psychological support, integrative therapy, and palliative care are all the potential aspects for the management of PCRP.
Successful recanalization of an acute occlusion of the left internal carotid artery and the left cerebral middle artery via the transbrachial approach: A case report
Authors: Xu Chao , Jin Tianyu , Wang Qinpu , Chen Danyu , Ying Jiangxian , Wang Peng
Published: August 2023

Introduction:

This case study presents an elderly patient with an acute ischemic stroke due to occlusion of the left internal carotid artery (ICA) and the left cerebral middle artery (MCA). The study aimed to evaluate the feasibility and effectiveness of a transbrachial approach for mechanical thrombectomy (MT) in patients with tandem occlusions.

Patient concerns:

The patient presented with stroke symptoms, including severe aphasia, right-sided facial palsy, left gaze deviation and right-sided weakness. The patient had a history of uncontrolled hypertension.

Diagnosis:

Diagnostic tests, including computed tomography and angiography, confirmed the presence of occlusions in both the left ICA and the left MCA.

Interventions:

The patient received MT bridging intravenous thrombolysis. When bilateral iliac arteries were found to be occluded, a puncture via the transbrachial approach was attempted. Angiography suggested an acute occlusion of both the left ICA and the left MCA. The C1 segment was inflated with a pre-dilated balloon and the thrombus in the M1 segment was removed successfully.

Outcomes:

Successful reperfusion was achieved, and the patient had a good outcome at discharge. No access-site complications were encountered.

Conclusion:

Transbrachial approach for MT, especially in those with tandem occlusions, is feasible and could provide an alternative to the transfemoral approach. This approach may be beneficial for patients with occlusions in multiple sites or with iliac artery occlusions. Further research is needed to evaluate the long-term effectiveness of this approach.
Strategies of improving adherence to lipid-lowering therapy in patients with atherosclerotic cardiovascular disease
Authors: Karalis Dean G.
Published: August 2023

Purpose of review

Lowering LDL-C has been shown to reduce ASCVD events, yet many ASCVD patients do not achieve their guideline-directed LDL-C goals leaving patients at increased risk of another ASCVD event. This review discusses implementation strategies to improve guideline-directed lipid management in patients with ASCVD focusing on the provider, patient, and system level.

Recent findings

At a provider level, under-prescribing of statin intensity due most often to statin intolerance, clinical inertia, insufficient monitoring of LDL-C levels, and the difficulty and cost of prescribing other lipid-lowering therapies such as the PCSK9 inhibitors leads to suboptimal cholesterol management in ASCVD patients. Patients concerns about medication side effects and lack of understanding of their ASCVD risk are causes of poor adherence to their lipid-lowering therapy as are barriers at a system level.

To improve cholesterol management in ASCVD patients will require an integrated approach targeting the provider, the patient and the system. There is a need for further education of clinicians on the importance of intensive LDL-C lowering in ASCVD patients and greater use of nonstatin LDL-C-lowering therapies for those patients on a maximally tolerated statin who have not achieved their guideline-directed LDL-C goal. This will require shared decision-making with a focus on patient education and patient–clinician communication so that the clinician's goals and aims align with that of the patient.
A new era in cystic fibrosis care: always changing and adapting
Authors: Diener Barry L. , Huertero Fredy , Stables-Carney Teresa , Hoelzer Maureen , Kier Catherine
Published: August 2023

Purpose of review

This review focuses on sharing the current and changing cystic fibrosis (CF) care model. This includes changes in CF care as a chronic disease with availability of new revolutionary, highly effective therapies as well as incorporation of shared decision-making, coproduction of care, quality improvement, telemedicine, and remote patient monitoring.

Recent findings

Changes in the CF management, the CF patient population, and CF care team are described as well as how CF care has adapted to these changes.

CF is a chronic, multisystem disease requiring a large specialized multidisciplinary care team for effective treatment. With improvements in CF care and new treatments, people with CF are living longer and healthier lives. As new issues arise, the CF team needs to adapt. This was highlighted by the introduction of highly effective cystic fibrosis transmembrane conductance regulator modulator therapy, which targets the cellular defect in CF, the COVID-19 pandemic, which lead to the incorporation of telehealth and remote patient monitoring into the CF care model, and the partnering with people with CF and families through shared decision-making and coproduction.
Yield of Postmortem Skeletal Surveys in Infants Presenting to Emergency Care With Sudden and Unexpected Death
Authors: Henry M. Katherine , Egbe Teniola I. , White Ammie M. , Servaes Sabah , Andronikou Savvas , Scribano Philip V. , Wood Joanne N.
Published: August 2023

Objectives

Child abuse should be considered in cases of sudden unexpected infant death (SUID). Postmortem skeletal surveys (PM-SS) are recommended to evaluate for abusive fractures in SUID. Little is known about the yield of PM-SS among infants presenting to emergency care with SUID. Our objectives were to (1) describe the presentation and care of infants with SUID at a tertiary children's hospital emergency department and (2) report PM-SS use and findings.

Methods

We performed a retrospective study of infants younger than 12 months with SUID presenting to an urban emergency department from 2007 to 2019. We describe their presentation and care, including PM-SS performance and findings, referrals to the medical examiner, and reports to child protective services (CPS). We assessed for associations between race, payer, and presentation with reports to CPS.

Results

Of 73 infants with SUID, concern for unsafe sleep was documented in 45 (61.6%) and 71 (97.3%) underwent cardiopulmonary resuscitation by a medical professional. All 73 (100%) underwent PM-SS and were referred to the medical examiner. Twelve definite fractures (11 rib, 1 classic metaphyseal lesion) and 8 possible fractures (7 rib, 1 classic metaphyseal lesion) were identified among 6 (8.2%) infants. Forty-three (58.9%) were reported to CPS. There were no associations between race, payer, age, or history of unsafe sleep and CPS reports.

Conclusions

One in 12 cases of SUID had a possible and/or definite fracture identified on plain radiography. Multicenter studies are needed to compare yield across different postmortem imaging modalities and populations.
Development, Implementation, and Provider Perception of Standardized Critical Event Debriefing in a Pediatric Emergency Department
Authors: Grither Allie , Leonard Kathryn , Whiteley Jill , Ahmad Fahd
Published: August 2023

Objective

Hot debriefings are communications among team members occurring shortly after an event. They have been shown to improve team performance and communication. Best practice guidelines encourage hot debriefings, but these are often not routinely performed. We aim to describe the development and implementation of a multidisciplinary hot debriefing process in our pediatric emergency department (ED), and its impact on hot debriefing completion and provider perceptions.

Methods

An internal tool and protocol for hot debriefings were developed by integrating responses from a survey of those who work in the ED at our institution and previously published debriefing tools. Charge nurses and pediatric emergency medicine physicians were trained to lead hot debriefings. Surveys on the perception of hot debriefings were administered before and 6 months postimplementation.

Twelve-month baseline data were established by asking physicians who cared for patients who died in the ED or within 48 hours of admission to recall debrief completion. Debriefs were then prospectively tracked for 6 months postimplementation.

Results

Debrief completion for patient deaths in the ED or within 48 hours of admission increased from 23% (5/22) to 75% (12/16) (P < 0.001). When assessing just those deaths within the ED, this number increased from 31% (5/16) to 85% (11/13) (P < 0.001).

There were 98 responses to a baseline survey (response rate, 60.5%). Most who were surveyed felt that debriefs rarely occurred, preferred hot debriefings to cold debriefings, and felt that more hot debriefings should occur. Perceived barriers included lack of time, interest, protocol, trained facilitators, departmental support, and inability to gather the team.

There were 88 responses to a postintervention survey (response rate, 56.8%), 50 of which had participated in a debrief and were included in analysis. Those surveyed felt that debriefs occurred more often and were more often valuable. Most perceived that barriers were significantly reduced. Most respondents felt that hot debriefs helped address systems issues and improved performance.

Conclusions

Implementation of a protocol for physician or charge nurse-led hot debriefings in our pediatric ED resulted in increased completion, perceived barrier reduction, and a uniform approach to address identified issues. Pediatric EDs should consider adoption of a hot debriefing protocol given these benefits.
A Case of Reactivated Acute Hepatitis in a 12-month-old Infant With Multiviral Infection, Including SARS-CoV-2 and Adenovirus
Authors: Dawood Jimmy , Wickersham Emily L. , Witmer Claire P. , Jones Milissa U.
Published: August 2023

Adenovirus hepatitis is of global concern due to its increasing incidence and poorly understood pathogenesis. Historically, adenovirus has contributed to the development of severe hepatitis in immunocompromised patients. The clinical course and management of such infections in previously healthy children remains elusive. We present a case of severe acute hepatitis in a previously healthy 12-month-old infant with a history of SARS-CoV-2 infection followed by multiviral infection including adenovirus. Additional evaluation revealed acute hepatitis without evidence of acute liver failure except for mild coagulopathy. She demonstrated clinical improvement with supportive therapy but later experienced reactivated hepatitis in the setting of a third new viral infection thereby warranting a second hospitalization. A liver biopsy was obtained due to concern for an underlying immunologic or metabolic etiology of her prolonged hepatitis. Our case provides insight into the medical management and clinical course of a previously healthy child with a history of SARS-CoV-2 and adenovirus infections leading to reactivated acute hepatitis.
Hepatitis C Virus Elimination Programs in Louisiana and Washington: Importance of Screening and Surveillance Systems
Authors: Talal Andrew H. , Dharia Arpan , Kapadia Shashi N. , Tyson Gia L. , Birch Susan , Zerzan-Thul Judy , Sullivan Donna , Britton Elizabeth , Wethington Elaine , Gonzalez Christopher J. , Fliss Mary , Mizroch Brandon , McCall Frederic , Lloyd Audrey R. , Shapiro Martin F. , Franco Ricardo
Published: August 2023

The US government has established a national goal of hepatitis C virus (HCV) elimination by 2030. To date, most HCV elimination planning and activity have been at the state level. Fifteen states presently have publicly available HCV elimination plans. In 2019, Louisiana and Washington were the first states to initiate 5-year funded HCV elimination programs. These states differ on motivation for pursuing HCV elimination and ranking on several indicators. Simultaneously, however, they have emphasized several similar elimination components including HCV screening promotion through public awareness, screening expansion, surveillance enhancement (including electronic reporting and task force development), and harm reduction. The 13 other states with published elimination plans have proposed the majority of the elements identified by Louisiana and Washington, but several have notable gaps. Louisiana's and Washington's comprehensive plans, funding approaches, and programs provide a useful framework that can move states and the nation toward HCV elimination.
Impact of Latent M. tuberculosis Infection Treatment on Time to CD4/CD8 Recovery in Acute, Recent, and Chronic HIV Infection
Authors: Grinsztejn Eduarda , Cardoso Sandra Wagner , Velasque Luciane , Hoagland Brenda , dos Santos Desiree Gomes , Coutinho Carolina , Cruz Silva Simone da Costa , Nazer Sandro Coutinho , Ferreira Ana Cristina Garcia , Castilho Jessica , Grinsztejn Beatriz , Veloso Valdilea G.
Published: August 2023

Introduction:

In people living with HIV, active and latent tuberculosis (TB) coinfections are associated with immune activation that correlate with HIV progression and mortality. We investigated the effect of initiating antiretroviral therapy (ART) during acute (AHI), recent (RHI), or chronic HIV infection (CHI) on CD4/CD8 ratio normalization and associated factors, the impact of latent TB infection treatment, and prior/concomitant TB diagnosis at the time of ART initiation.

Methods:

We included sex with men and transgender women individuals initiating ART with AHI, RHI and CHI between 2013 and 2019, from a prospective cohort in Brazil. We compared time from ART initiation to the first normal CD4/CD8 ratio (CD4/CD8 ≥1) using Kaplan–Meier curves and multivariable Cox proportional hazards models. Sociodemographic and clinical variables were explored. Variables with P-values <0.20 in univariable analyses were included in multivariable analyses.

Results:

Five hundred fifty participants were included, 11.8% classified as AHI and 6.4% as RHI, 46.7% with CHI-CD4 cell counts ≥350 cells/mm3 and 35.1% with CHI-CD4 cell counts <350 cells/mm3. Time to normalization was shortest among AHI patients, followed by RHI and CHI individuals with higher baseline CD4. In the multivariable model, AHI was associated with a six-fold increased likelihood of achieving a CD4/CD8 ratio ≥1 (hazard ratio [HR]: 6.03; 95% confidence interval [CI]: 3.70 to 9.82; P < 0.001), RHI with HR: 4.47 (95% CI: 2.57 to 7.76; P < 0.001), and CHI CD4 ≥350 cells/mm3 with HR: 1.87 (95% CI: 1.24 to 2.84; P = 0.003). Latent TB infection treatment was significantly associated with a higher likelihood of the outcome (HR: 1.79; 95% CI: 1.22 to 2.62; P = 0.003). Previous history or concomitant active TB at ART initiation was associated with a lower likelihood of the outcome (HR: 0.41; 95% CI: 0.16 to 1.02; P = 0.054).

Conclusions:

Initiating ART early during AHI may offer an opportunity to mitigate immune damage. Efforts to implement HIV diagnosis and ART initiation during AHI are critical to amplify ART benefits.
Orbital Apex Syndrome Caused by Intraorbital Aspergillus Infection
Authors: Lu Tianju , Chen Xiao-Hu , Dai Yan
Published: August 2023

Orbital apex syndrome, a clinical disease that is uncommon and has a high fatality rate. Tumor, endocrine, and inflammatory variables are frequently responsible for its occurrence. The authors describe a 53-year-old Chinese man who was diagnosed with orbital apex syndrome and coupled type 2 diabetes mellitus and a fungus infestation. Treatment included nasal endoscopic orbital apical decompression, anti-infection, and adequate debridement. Except for inevitable optic nerve damage, postoperative proptosis and headache manifestations improved, and systemic infection was timely contained with no signs of recurrence or serious complications occurred. The orbital apex syndrome is difficult to treat, and soon as possible biopsy of the lesion, aggressive surgical decompression, and antifungal treatment seem to be effective ways to improve survival rates.
NOVEL PS-OME MIRNA130B-3P REDUCES INFLAMMATION AND INJURY AND IMPROVES SURVIVAL AFTER RENAL ISCHEMIA-REPERFUSION INJURY
Authors: Vazquez Gustavo , Sfakianos Maria , Coppa Gene , Jacob Asha , Wang Ping
Published: August 2023

Introduction: Acute kidney injury (AKI) is a prevalent medical disorder characterized by a sudden decline in kidney function, often because of ischemia/reperfusion (I/R) events. It is associated with significant chronic complications, and currently available therapies are limited to supportive measures. Extracellular cold-inducible RNA-binding protein (eCIRP) has been identified as a mediator that potentiates inflammation after I/R injury. However, it has been discovered that miRNA 130b-3p acts as an endogenous inhibitor of eCIRP. To address the inherent instability of miRNA in vivo, a chemically modified miRNA mimic called PS-OME miR130 was developed. We hypothesize that administration of PS-OME miR130 after renal I/R can lead to reduced inflammation and injury in a murine model of AKI. Methods: C57BL/6 male mice underwent renal I/R by clamping of bilateral renal hilum for 30 min or sham operation. Immediately after closure, mice were intravenously administered vehicle (phosphate-buffered saline) or PS-OME miR130 at a dose of 12.5 nmol/mouse. Blood and kidneys were collected after 24 h for further analysis. Separately, mice underwent renal I/R and administered vehicle or treatment and, survival was monitored for 10 days. Results: After renal I/R, mice receiving vehicle showed a significant increase in serum markers of kidney injury and inflammation including blood urea nitrogen, NGAL, KIM-1, and IL-6. After treatment with PS-OME miR130, these markers were significantly decreased. Kidney tissue mRNA expression for injury and inflammation markers including NGAL, KIM-1, KC, and MIP-2 were increased after renal I/R; however, these markers showed a significant reduction with PS-OME miR130 treatment. Histologically, treatment with PS-OME miR130 showed a significant decrease in neutrophil infiltration and injury severity score, and decreased apoptosis. In the 10-day survival study, mice in the treatment group showed a significant reduction in mortality as compared with vehicle group. Conclusion: In a murine renal I/R model, the administration of PS-OME miR130, a direct eCIRP antagonistic miRNA mimic, resulted in the reduction of kidney inflammation and injury, and improved survival. PS-OME miR130 holds promise to be developed as novel therapeutic for AKI as an adjunct to the standard of care.
Overexpressing the IPT gene improves drought tolerance and nutritional value of tropical maize (Zea maysL.)
Authors: Muruo Rose Mweru , Nchore Shem B. , Oduor Richard O. , Ngugi Mathew Piero
Published: August 2023

Drought stress poses a significant threat to crop productivity, making the development of drought-tolerant crops a priority. The impact of drought on grain yield loss varies significantly, ranging from 10% to 76%, depending on the specific stage of occurrence and the severity of the drought. In this study, we investigated the effects of introducing the pSARK::IPT transgene on the drought tolerance and nutritional composition of successive generations of tropical maize. Towards this goal, we screened different generations of maize plants by genotyping PCR, exposed them to long term drought stress and analysed several drought stress markers and nutritional profiles of the plants. Our results demonstrated that the pSARK::IPT transgene was present in 4 successive generations of maize plants. Under drought conditions, transgenic maize exhibited higher relative water content, and delayed senescence compared to wild-type plants. Additionally, transgenic plants showed increased levels of total chlorophyll, chlorophyll a, and chlorophyll b, indicating improved photosynthetic activity under water deficit. Our study also showed that IPT-transgenic plants produced substantially higher yields and demonstrated enhanced nutritional value compared to wildtype plants when grown under well-watered conditions. Further research is warranted to investigate the underlying molecular mechanisms involved in these improvements and assess the performance of pSARK::IPT maize under field conditions.
Advancing EDGE Zones: spatial priorities for the conservation of tetrapod evolutionary history
Authors: Pipins Sebastian , Baillie Jonathan E.M. , Bowmer Alex , Pollock Laura J. , Owen Nisha , Gumbs Rikki
Published: August 2023

The biodiversity crisis is set to prune the Tree of Life in a way that threatens billions of years of evolutionary history. To secure this evolutionary heritage along with the benefits it provides to humanity, there is a need to understand where in space the greatest losses are predicted to occur. We therefore present threatened evolutionary history mapped for all tetrapod groups, globally and within Biodiversity Hotspots, and identify priority regions of Evolutionarily Distinct and Globally Endangered (EDGE) species at both a grid cell and national level. We find that threatened evolutionary history peaks in Cameroon, whilst EDGE species richness peaks in Madagascar. We refined and advanced the 2013 EDGE Zone concept for spatially prioritising phylogenetic diversity using a novel complementarity procedure with uncertainty incorporated for 33,628 tetrapod species. This involved using extinction risk, phylogenetic, and spatial data to iteratively select areas with the highest accumulated threatened evolutionary history driven by unique species compositions. We identify 25 priority EDGE Zones, which are insufficiently protected and disproportionately exposed to high levels of human pressure. Together, the 25 EDGE Zones occupy 0.723% of the world’s surface but harbour one-third of the world’s threatened evolutionary history, half of which is endemic to these grid cells. They also contain part of the distribution of 918 EDGE tetrapod species, representing near one-third of all EDGE species, with 480 being endemic. Our tetrapod EDGE Zones highlight areas of immediate concern for researchers, practitioners, policymakers, and communicators looking to safeguard the Tree of Life.
Molecular dynamics analyses of CLDN15 pore size and charge selectivity
Authors: McGuinness Sarah , Li Pan , Li Ye , Fuladi Shadi , Konar Sukanya , Sajjadi Samaneh , Sidahmed Mohammed , Li Yueying , Shen Le , Araghi Fatemeh Khalili , Weber Christopher R.
Published: August 2023

The Claudin-15 (CLDN15) channel is important for nutrient, electrolyte, and water transport in the gastrointestinal tract. We used cell culture studies and molecular dynamics simulations to elucidate its structure and permeability mechanisms. We provide a model that underscores the crucial role of the D55 residue in the CLDN15 selectivity filter, which interacts with permeating cations. Our studies demonstrated the mechanisms whereby the size and charge of the D55 residue influence paracellular permeability. By altering D55 to larger, negatively charged glutamic acid (E) or similarly sized neutral asparagine (N), we observed changes in pore size and selectivity, respectively. D55E mutation decreased pore size, favoring small ion permeability without affecting charge selectivity, while D55N mutation led to reduced charge selectivity without markedly altering size selectivity. These findings shed light on the complex interplay of size and charge selectivity of CLDN15 channels. This knowledge can inform the development of strategies to modulate the function of CLDN15 and similar channels, which has implications for tight junction modulation in health and disease.

Using cell culture and molecular dynamics simulations, we have clarified the role of amino acid D55 in the claudin-15 channel function. D55 is important for channel permeability and selectivity in both charge- and size-selective manners. This insight into the structural determinant of claudin cation channel function provides potential insight for designing approaches to alter the claudin channel function to benefit human health.
Trans-Omics analysis of post injury thrombo-inflammation identifies endotypes and trajectories in trauma patients
Authors: Cohen Mitchell J. , Erickson Christopher B. , Lacroix Ian S. , Debot Margot , Dzieciatkowska Monika , Mitra Sanchayita , Schaid Terry R. , Hallas William M. , Thielen Otto N. , Cralley Alexis L. , Banerjee Anirban , Moore Ernest E , Silliman Christopher C. , D’Alessandro Angelo , Hansen Kirk C.
Published: August 2023

Understanding and managing the complexity of trauma-induced thrombo-inflammation necessitates an innovative, data-driven approach. This study leveraged a trans-omics analysis of longitudinal samples from trauma patients to illuminate molecular endotypes and trajectories that underpin patient outcomes. We hypothesized that trans-omics profiling reveals underlying clinical differences in severely injured patients that may present with similar clinical characteristics but ultimately have different responses to treatment and outcomes. Here we used proteomics and metabolomics to profile 759 of longitudinal plasma samples from 118 patients at 11 time points and 97 control subjects. Patients were stratified by shock and injury severity, revealing a spectrum of responses to trauma and treatment that are fundamentally tied to their unique underlying biology. Ensemble models were employed, demonstrating the predictive power of these molecular signatures with area under the receiver operating curves of 80 to 94% for key outcomes such as death. Then, transomics-based patient states were defined to create a map of unique pathophysiologic states encountered by trauma patients across time. Last, distinct longitudinal patient trajectories were identified that group patients according to their path through trauma transomics state maps. Unsupervised clustering of longitudinal trans-omics data identified specific clinical phenotypes while omics-based trajectories increased resolution on outcome prediction. The molecularly defined endotypes and trajectories provide an unprecedented lens to understand and potentially guide trauma patient management, opening a path towards precision medicine. This strategy presents a transformative framework that aligns with our understanding that trauma patients, despite similar clinical presentations, might harbor vastly different biological responses and outcomes.

One-sentence summary

Transomic analyses of longitudinal plasma samples from severely injured patients identifies endotypes and trajectories that predict clinical outcomes.
Replication and Refinement of Brain Age Model for adolescent development
Authors: Ray Bhaskar , Chen Jiayu , Fu Zening , Suresh Pranav , Thapaliya Bishal , Farahdel Britny , Calhoun Vince D. , Liu Jingyu
Published: August 2023

The discrepancy between chronological age and estimated brain age, known as the brain age gap, may serve as a biomarker to reveal brain development and neuropsychiatric problems. This has motivated many studies focusing on the accurate estimation of brain age using different features and models, of which the generalizability is yet to be tested. Our recent study has demonstrated that conventional machine learning models can achieve high accuracy on brain age prediction during development using only a small set of selected features from multimodal brain imaging data. In the current study, we tested the replicability of various brain age models on the Adolescent Brain Cognitive Development (ABCD) cohort. We proposed a new refined model to improve the robustness of brain age prediction. The direct replication test for existing brain age models derived from the age range of 8-22 years onto the ABCD participants at baseline (9 to 10 years old) and year-two follow-up (11 to 12 years old) indicate that pre-trained models could capture the overall mean age failed precisely estimating brain age variation within a narrow range. The refined model, which combined broad prediction of the pre-trained model and granular information with the narrow age range, achieved the best performance with a mean absolute error of 0.49 and 0.48 years on the baseline and year-two data, respectively. The brain age gap yielded by the refined model showed significant associations with the participants’ information processing speed and verbal comprehension ability on baseline data.
A universal preservation protocol for multi-omic and histological analysis of kidney tissue
Authors: Gies Sydney E. , Hänzelmann Sonja , Kylies Dominik , Lagies Simon , Lassé Moritz , Hausmann Fabian , Khatri Robin , Poets Manuela , Zhang Tianran , Lu Shun , Liu Shuya , Chilla Silvia , Edenhofer Ilka , Czogalla Jan , Braun Fabian , Kammerer Bernd , Rinschen Markus M. , Puelles Victor G. , Bonn Stefan , Lindenmeyer Maja T. , Huber Tobias B.
Published: August 2023

Biobanking of tissue from clinically obtained kidney biopsies for later use with multi-omic and imaging techniques is an inevitable step to overcome the need of disease model systems and towards translational medicine. Hence, collection protocols ensuring integration into daily clinical routines using preservation media not requiring liquid nitrogen but instantly preserving kidney tissue for clinical and scientific analyses are of paramount importance. Thus, we modified a robust single nucleus dissociation protocol for kidney tissue stored snap frozen or in the preservation media RNAlaterand CellCover. Using porcine kidney tissue as surrogate for human kidney tissue, we conducted single nucleus RNA sequencing with the Chromium 10X Genomics platform. The resulting data sets from each storage condition were analyzed to identify any potential variations in transcriptomic profiles. Furthermore, we assessed the suitability of the preservation media for additional analysis techniques (proteomics, metabolomics) and the preservation of tissue architecture for histopathological examination including immunofluorescence staining. In this study, we show that in daily clinical routines the RNAlaterfacilitates the collection of highly preserved kidney biopsies and enables further analysis with cutting-edge techniques like single nucleus RNA sequencing, proteomics, and histopathological evaluation. Only metabolome analysis is currently restricted to snap frozen tissue. This work will contribute to build tissue biobanks with well-defined cohorts of the respective kidney disease that can be deeply molecularly characterized, opening new horizons for the identification of unique cells, pathways and biomarkers for the prevention, early identification, and targeted therapy of kidney diseases.
Inferring genetic structure of European beech from observations of spectral phenotypes
Authors: Czyż Ewa A. , Schmid Bernhard , Eppinga Maarten B. , de La Harpe Marylaure , Moradi Aboubakr , Li Cheng , Schaepman Michael E. , Schuman Meredith C.
Published: August 2023

Biodiversity loss presents a growing threat to the global environment and requires systematic and spatially contiguous monitoring. Monitoring of within-species genetic variation, a key factor when assessing biodiversity loss, is laborious and could be complemented by observations of phenotypes allowing inferences about genetic variation. We studied genetic and phenotypic variations in the common European beech (Fagus sylvaticaL.) derived from whole-genome sequences and spectral phenotypes of more than 200 individuals at 22 sites across the species’ natural range. The spectral phenotypes were collected under standardized illumination/observation conditions from the same top-of-canopy leaves used for nuclear DNA extraction. We found that spectral and environmental information explains 77.7% of the variance along the first two Principal Coordinates representing genetic structure among sampled individuals. Information from spectral phenotypes contributed 12.1% to predictions of between-site genetic structure. We therefore conclude that future remote observations having sufficient spectral and spatial resolution could improve our ability to rapidly and continuously monitor genetic diversity in trees.

Highlights

Genetic diversity underpins biodiversity which loss requires systematic monitoring

Spectral phenotypes acquiredin situare indicative of genetic variation

Intraspecific spectral and genomic variation correlate across a species range

Spectral phenotypes improve prediction of the between-site genetic structure

Remote observations may contribute to monitoring genetic diversity within species
Generation of “OP7 chimera” defective interfering particle preparations free of infectious influenza A virus that shows antiviral efficacy in mice
Authors: Dogra Tanya , Pelz Lars , Boehme Julia D. , Küchler Jan , Kershaw Olivia , Marichal-Gallardo Pavel , Bälkner Maike , Hein Marc D. , Gruber Achim D. , Benndorf Dirk , Genzel Yvonne , Bruder Dunja , Kupke Sascha Y. , Reichl Udo
Published: August 2023

Influenza A virus (IAV) defective interfering particles (DIPs) are considered as new promising antiviral agents. Conventional DIPs (cDIPs) contain a deletion in the genome and can only replicate upon co-infection with infectious standard virus (STV), during which they suppress STV replication. We previously discovered a new type of IAV DIP “OP7” that entails genomic point mutations and displays higher antiviral efficacy than cDIPs. To avoid safety concerns for the medical use of OP7 preparations, we developed a production system that does not depend on infectious IAV. We reconstituted a mixture of DIPs consisting of cDIPs and OP7 chimera DIPs, in which both harbor a deletion in their genome. To complement the defect, the deleted viral protein is expressed by the suspension cell line used for production in shake flasks. Here, DIP preparations harvested are not contaminated with infectious virions, and the fraction of OP7 chimera DIPs depended on the multiplicity of infection. Intranasal administration of OP7 chimera DIP material was well tolerated. A rescue from an otherwise lethal IAV infection and no signs of disease upon OP7 chimera DIP co-infection demonstrated the remarkable antiviral efficacy. The clinical development of this new class of broad-spectrum antiviral may contribute to pandemic preparedness.