bluuebunny/crossref_metadata_2025 huggingface dataset:
C53. Infection of Coronavirus Disease 2019 Reveals Brugada Pattern
Authors: Patriya N A S , Yasa A
Published: March 2023

Background

Coronavirus Disease 2019 (COVID-19) resulted considerable morbidity and mortality worldwide since December 2019. In the other hand, Brugada syndrome had higher risk of sudden cardiac death. Although it was manifested with an electrocardiographic (EGC) abnormalities, the patients with Brugada syndrome were often healthy and unaware of their genetic predisposition.

Case Summary

A 59 years old man without significant medical history was reported a day of fever, productive cough, and shortness of breath. He did not complain any chest pain, palpitation, and episode of syncope. The patient had no family history of sudden cardiac death. On presentation, he was febrile (39,5°C), tachycardia (110 beats/ min), and tachypnea (28 breath/ min). Laboratory findings of the patient were elevated High-sensitivity C-reactive protein (hs-CRP), with normal electrolyte level, and troponin. The Polymerase chain reaction (PCR) test for COVID-19 performed with the positive result. The chest radiograph showed multifocal bilateral interstitial with a normal cardiac silhouette. The ECG revealed Brugada type 2 ECG pattern. A bedside echocardiogram demonstrated with the normal result. His condition continued to improve and the ECG demonstrated complete resolution of the initial Brugada ECG pattern.

Discussion

COVID-19 infection has been described as unmasking Brugada pattern. The most frequently reported symptoms of COVID-19 was fever. Brugada syndrome was a genetic disorder, that was most commonly involving SCN5A gene, which encoded the cardiac sodium channel. Fever caused blockade of sodium channel was being well described provocative trigger that might incite arrhythmia in patient with Brugada syndrome.
C64. New Onset PVC Bigeminy Post Covid-19 Infection: Another Covid-Cardiac Related Problem
Authors: Jeremiah B , Lubis A C , Hasan H
Published: March 2023

Background

Covid-19 is an infectious disease caused by a newly discovered coronavirus that caused acute severe respiratory syndrome and other complication. Many cardiac complication already occurred such as carditis and acute heart failure. PVC bigeminy is a new complication that we found in our post covid-19 patient.

Case Summary

A 31-years-old female patient admitted to the outpatient department with chief complaint palpitation with chest discomfort in the past 1 month with a history covid-19 infection 3 months ago with prolong covid infection for 2 months. ECG showed sinus rhythm and bigeminy PVC with PVC LBBB morphology left inferior axis and transition zone in V4. The patient planned to do Electrophysiology study and ablation. From the EP study we found 2 type of PVC, both of the PVC have LBBB morphology with left inferior axis and transitional zone in V4. The first PVC had 42ms earliest activation time and the second PVC had 48ms earliest activation. We do ablation with non irrigating catheter on the first PVC but the PVC still remain. Then try with irrigating catheter and do the ablation. After the ablation the PVC already vanished and the ablation was successful.

Discussion

PVC bigeminy post covid-19 infection is a rare complication in covid-19 patient. PVC bigeminy cause several complain from palpitation, chest discomfort, and shortness of breath. Ablation is one of the best way to treat PVC bigeminy patient with symptoms and in the patient the ablation was successful.
C65. Pace and Ablate as an Alternative Approach for Rate Control Strategy in Patient with Atrial Fibrillation
Authors: Hazzy Fandy , Rizal Ardian
Published: March 2023

Background

AF patient with refractory to optimal medical therapy for rate or rhythm control, atrioventricular (AV) nodal ablation with permanent pacemaker (PPM) implantation is an effective strategy for symptomatic relief. Maintenance of controlled ventricular rate helps to avoid frequent exacerbations of CHF and tachycardia-mediated cardiomyopathy, and is also associated with improved quality of life.

Case Summary

Female 66-year-old suffered from Heart Failure exacerbations caused by paroxysmal AF with rapid ventricular response (RVR) with underlying hypertensive cardiovascular disease. Rhythm control strategy with drip Amiodarone induce sinus bradycardia with unstable hemodynamic, when drugs was stopped then AF RVR reappeared, we tried to rate control strategy with Digoxin but, she experienced same condition as before. She underwent a pragmatical technique AV nodal ablation with cardiac pacing for rate control and she had drastic improvement of symptoms within the next 24 h. Complete AV block was achieved after application of 2 radiofrequency energies over the anatomic AV node. A permanent pacemaker (PPM) was programmed to VVIR at the rate of 70 bpm.

Discussion

Conventional medical therapies, including beta-blockers, non-dihydropyridine calcium channel blockers, digoxin, and anti-arrhythmic drugs, may fail to control the ventricular rate. Atrioventricular junction ablation and pacing (AVJAP) can be applied for patients whom medication is inadequate or associated with side effects (Recommendation IIA). According to our case, AVJAP is possible but an attractive choice for some elderly patients who are not compliant with treatment or associated with dangerous side effect for patients.
C70. Performing Percutaneous Coronary Intervention in Dextrocardia: A Case Report
Authors: Syafar R H , Khairat M , Syukri M
Published: March 2023

Background

Dextrocardia is defined as the heart location in the right hemithorax with the apex pointing inferiorly and to the right. Performing percutaneous coronary intervention (PCI) in patient with dextrocardia can be difficult and requires some modification.

Case Summary

A 55-years old male with chest pain 3 hours before admission, apex in right side, a chest X-ray confirm the heart in the right hemithorax, electrocardiogram (ECG) was consistent with dextrocardia and showed inferior ST-segment elevation myocardial infarction (STEMI). We performed primary PCI with femoral access. During coronary angiography, it was a challenge to engage the diagnostic catheter to both of ostium right and left coronary artery. Coronary angiography showed total occlusion in the proximal of right coronary artery (RCA). We inversed the engagement technique and radiological angles for RCA from the left anterior oblique 35º to the right anterior oblique 30º and finally revascularization could be done easier.

Discussion

Performing PCI in patient with dextrocardia can be challenging. Inversion the engagement technique and radiological angles and views will give an advantage to the operator for imaging and doing intervention. Using image reversal technology is also help to get the image like a normal position.
C72. Peripartum Cardiomyopathy: “Comparison in Management of Two Cases”
Authors: Widyastuti W , Krevani C K , Karani Y
Published: March 2023

Background

Peripartum cardiomyopathy (PPCM) is a pregnancy related cardiomyopathy that associated with high morbidity, mortality, also high probability of partial and often full recovery. The management of PPCM remains challenging.

Case Summary

The first patient was 33 years old woman, diagnosed with PPCM 3 days after giving birth. The second patient was 30 years old woman with heart failure symptoms since 3 months after giving birth but only seek medical attention 10 months later. Both patients presented with heart failure and LVEF 37%. The difference was acute onset PPCM on the first patient and the second one was already fall to chronic heart failure condition due to untreated PPCM. Both patients were treated with heart failure drugs but no bromocriptine in second patient. Six months follow up showed increased LVEF to 65% in first patient with full recovery but no significant improvement on second patient with LVEF 40 %.

Discussion

The first patient was presented as acute PPCM. Diagnosis PPCM in the second patient was made after exclusion of other causes of heart failure. Both women presenting after delivery, so can generally be treated according to the ESC Guidelines for heart failure. BOARD scheme therapy (Bromocriptine, Oral heart failure therapies, Anticoagulants, vasoRelaxing agents, Diuretic) were used in first patient but we treated the second patient as common heart failure patient without including bromocriptine in therapy. Full recovery found in patient that was diagnosed and treated earlier. Long term management and counselling is essential for these patients.
C73. Phlegmasia Cerulea Dolens "A Case of the Blue Leg": Act Properly, Avoid Morbidity and Mortality
Authors: Dewi I P , Wardhani L F K , Budiarto R M
Published: March 2023

Background

Deep vein thrombosis (DVT) may compromise venous outflow from a limb, causing significant swelling. Phlegmasia cerulea dolens (PCD) is a severe presentation of massive DVT. PCD is a medical emergency that can lead to venous gangrene of the lower extremity. Early diagnosis and prompt treatment are crucial for limb salvage.

Case Presentation

We report 65-year-old woman presented with acute onset edema and pain in left leg. Left lower limb examination found edema from the left groin to the distal left extremity, marmorata, and bullae with cold palpation. Sensoric and motoric function of left leg were decrease. Duplex ultrasonography showed thrombus and non compressible in left common femoral vein (CFV). We have done systemic thrombolytic using streptokinase 250.000 IU. However, the condition of the patient didn’t improve. The patient then underwent surgical thrombectomy procedure with a forgaty catheter. There was a ± 20 cm of thrombus. Her left lower limb became warm after thrombectomy and her symptoms improved. Finally, after 12 days hospitalization the patient was discharged and give anticoagulant therapy.

Conclusion

Although uncommon, it is important to identify patients with PCD because they should be considered for more aggressive management. Intravenous anticoagulant is one of therapeutic strategy while a decision to pursue more aggressive therapy is being considered. Patients with extensive DVT but without signs of PCD do not routinely receive thrombolysis but should be anticoagulated and monitored closely for the development of PCD.
C75. Premature Coronary Artery Disease in Young Male Patient with Strong Family History
Authors: Kurniawan A , Rohman M S
Published: March 2023

Background

Coronary artery disease (CAD) occurring in less than 45 years of age is termed as premature CAD (PCAD). Recent studies showed a prevalence of 4-10 % of PCAD. PCAD is associated with unfavorable outcomes for the patients and had a greater impact on the quality of life. Family History is the best method to explained complex interaction between shared risk factor.

Case Summary

A 37-years old male admitted to Saiful Anwar Hospital for further evaluation of anginal pain. The patient complains of recurrent chest pain since 5 months ago but still relieved by rest. The electrocardiogram showed Wellens Type B which is specific for critical stenosis of the left anterior descending artery (LAD). Then the patient undergoing DCA Ad Hoc. The implantation of a 46 mm DES at proximal until distal LAD was performed. The patient discharged after a day observation.

Discussion

The challenging point, in this case, was it happen at a young age with strong family history. There was positive family history of PCAD in 1st degree relative on her brother and mother, despite several risk factors were identified in this case consist of smoking, and dyslipidemia, which make CAD risk higher. Despite adequate control of risk factors, family screening is important to reveal subclinical atherosclerosis.
C77. Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction with Acute Kidney Injury caused by Cardiogenic Shock, Is it Really Safe?: A Case Report
Authors: Pamuna O S , Rohman M S
Published: March 2023

Background

ST-elevation myocardial infarction (STEMI) is a life-threatening condition. Timely treatment with Percutaneous Coronary Intervention (PCI) is a recommended management of STEMI. However, PCI in STEMI with Acute Kidney Injury (AKI) was a high-risk procedure with possibilities of worsening renal function.

Case Description

A 53 years old, woman, was referred from a private hospital with STEMI inferior Killip IV onset 5 hours with typical chest pain and azotemia. Creatinine serum was 3.4 mg/dl; eGFR 15 ml/m/1.73m2. Blood Gas Analyses show metabolic acidosis uncompensated. In the emergency room, she got hydration and inotropic drugs. After the PCI procedure, she was fallen into an altered mental status and shock condition. The laboratorium result in our hospital showed improvement of creatinine level to 1.6 mg/dl. We treated this patient for 9 days, with optimal medicaments and fluid therapy. On the last day of treatment, there is an improvement in clinical presentation and laboratorium results.

Discussion

STEMI is a life-threatening condition caused by acute occlusion in the coronary artery. The guideline strongly recommended Primary Percutaneous Coronary Intervention in a patient with STEMI and cardiogenic shock. AKI in STEMI patients was a consequence of acute cardiac condition and its treatment. PPCI in AKI condition can improve renal function due to improvement of renal flow. But on the other side, it can worsen renal function due to contrast-related acute kidney injury. Proper management to prevent worsening of renal function is very important.
What can we learn from Australian general practices taking steps to be more environmentally sustainable? A qualitative study
Authors: Pavli Alex , Loblay Victoria , Rychetnik Lucie , Usherwood Tim
Published: March 2023

Background

Climate change is impacting the health of individuals worldwide. At the same time, the healthcare sector contributes to carbon emissions. In Australia, healthcare contributes 7% of the country’s carbon footprint. Research into the environmental impact and mitigation of carbon emissions in primary care is an emerging area.

Objective

To explore staff perspectives on facilitators and barriers to environmental sustainability in 3 Australian general practices seeking to reduce their environmental impact.

Methods

We used a qualitative, case-study approach, conducting 23 semistructured interviews with staff across the 3 practices including nurses, administrative staff, and doctors. Observation of systems and staff behaviour relating to environmental sustainability was undertaken at 1 practice. Thematic analysis was conducted to determine themes relating to factors influencing the implementation of environmentally sustainable initiatives within practice settings.

Results

Climate mitigation efforts raised by participants were largely focussed on energy and waste reduction, rather than prescribing pharmaceuticals and staff and patient transport. Three main factors influencing change towards sustainable practice were identified: “Leadership,” “Staff Engagement and Workplace Culture,” and “Concomitant Benefits.” A leadership team and workplace culture that valued environmental sustainability were found to be important facilitators, as were concomitant benefits, in particular financial savings. Barriers included what interviewees described as a lack of knowledge about initiatives with the highest impact, lack of understanding described by staff of the evidence behind particular initiatives, waning staff engagement and infection control concerns.

Conclusions

Our research highlights several important factors that contribute to the implementation of intended environmentally sustainable initiatives in these 3 practices. Further education, research and high-level policy guidance on the potential environmental impact of prescribing pharmaceuticals, staff and patient transport and unnecessary tests and treatments are recommended to further promote environmental sustainability in primary care.
Examining the Causal Mediating Role of Cardiovascular Disease on the Effect of Subclinical Cardiovascular Disease on Cognitive Impairment via Separable Effects
Authors: Andrews Ryan M , Shpitser Ilya , Didelez Vanessa , Chaves Paulo H M , Lopez Oscar L , Carlson Michelle C
Published: March 2023

Background

An important epidemiological question is understanding how vascular risk factors contribute to cognitive impairment. Using data from the Cardiovascular Health Cognition Study, we investigated how subclinical cardiovascular disease (sCVD) relates to cognitive impairment risk and the extent to which the hypothesized risk is mediated by the incidence of clinically manifested cardiovascular disease (CVD), both overall and within apolipoprotein E-4 (APOE-4) subgroups.

Methods

We adopted a novel “separable effects” causal mediation framework that assumes that sCVD has separably intervenable atherosclerosis-related components. We then ran several mediation models, adjusting for key covariates.

Results

We found that sCVD increased overall risk of cognitive impairment (risk ratio [RR] = 1.21, 95% confidence interval [CI]: 1.03, 1.44); however, there was little or no mediation by incident clinically manifested CVD (indirect effect RR = 1.02, 95% CI: 1.00, 1.03). We also found attenuated effects among APOE-4 carriers (total effect RR = 1.09, 95% CI: 0.81, 1.47; indirect effect RR = 0.99, 95% CI: 0.96, 1.01) and stronger findings among noncarriers (total effect RR = 1.29, 95% CI: 1.05, 1.60; indirect effect RR = 1.02, 95% CI: 1.00, 1.05). In secondary analyses restricting cognitive impairment to only incident dementia cases, we found similar effect patterns.

Conclusions

We found that the effect of sCVD on cognitive impairment does not seem to be mediated by CVD, both overall and within APOE-4 subgroups. Our results were critically assessed via sensitivity analyses, and they were found to be robust. Future work is needed to fully understand the relationship between sCVD, CVD, and cognitive impairment.
“City by city:” reclaiming people of color voices through the Narrative Justice Project
Authors: Grant Rachel , Wakeman Vanessa
Published: March 2023

The Narrative Justice Project (NJP) challenges master narratives and creates more complex understandings by delving into the human-interest aspects of mass communications. For people of color (POC), the mass media is a racialized tool used in the historical context to justify the lack of rights or equality. This study illustrates how counter-stories function as a redefinition of humanity. The NJP training presents those communication values for POC to understand how to explain their complex narratives while also giving communities the ability to advocate for themselves. Utilizing observation and focus groups, this study examined how public interest communication campaigns generate conversations that challenge hegemonic thinking of who is accepted into the public.
Hodge Theory for Polymatroids
Authors: Pagaria Roberto , Pezzoli Gian Marco
Published: March 2023

We construct a Leray model for a discrete polymatroid with arbitrary building set and we prove a generalized Goresky–MacPherson formula. The first row of the model is the Chow ring of the polymatroid; we prove Poincaré duality, Hard Lefschetz, and Hodge–Riemann theorems for the Chow ring. Furthermore, we provide a relative Lefschetz decomposition with respect to the deletion of an element.
Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients
Authors: Heil Emily L , Claeys Kimberly C , Kline Ellen G , Rogers Tara M , Squires Kevin M , Iovleva Alina , Doi Yohei , Banoub Mary , Noval Mandee M , Luethy Paul M , Shields Ryan K
Published: March 2023

Objectives

We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates.

Materials and methods

Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively.

Results

Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations.

Conclusions

Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.
222-nm UVC light as a skin-safe solution to antimicrobial resistance in acute hospital settings with a particular focus on methicillin-resistant Staphylococcus aureus and surgical site infections: a review
Authors: Panzures Alexis
Published: March 2023

The increasing burden of antimicrobial resistance necessitates a novel approach to disinfect multidrug resistant pathogens. Conventional 254-nm ultraviolet-C (UVC) light shows high germicidal efficacy against bacteria. However, it induces pyrimidine dimerization in exposed human skin with carcinogenic potential. Recent developments suggest 222-nm UVC light can be used to disinfect bacteria and cause less harm to human DNA. This new technology can be used to disinfect healthcare-associated infections and more specifically surgical site infections (SSIs). This includes but is not limited to methicillin-resistant Staphylococcus aureus (MRSA), P. aeruginosa, C. difficile, E. coli, and other aerobic bacteria. This thorough review of scarce literature assesses the germicidal efficacy and skin safety of 222-nm UVC light with a particular focus on its clinical applications to MRSA and SSIs. The study reviews a variety of experimental models, including in vivo and in vitro cell cultures, live human skin, human skin models, mice skin, and rabbit skin. The potential for long-term eradication of bacteria and efficacy against specific pathogens is appraised. This paper focuses on the methods and models used in past and present research to determine the efficacy and safety of 222-nm UVC in the acute hospital setting with a focus on MRSA and its applicability to SSIs.
Deep learning-based framework for monitoring wearing personal protective equipment on construction sites
Authors: Lee Yeo-Reum , Jung Seung-Hwan , Kang Kyung-Su , Ryu Han-Cheol , Ryu Han-Guk
Published: March 2023

The construction site is one of the most dangerous industries because the number of occupational injuries and fatalities is significantly higher compared to other industries. Proper use of personal protective equipment (PPE) by workers can reduce the risk of occupational injuries and fatalities. However, for a variety of reasons, workers tend not to wear their PPEs properly. To address these issues, we propose a vision-based framework for monitoring wearing PPE. The developed framework is based on the real-time pixel-level detect model YOLACT, which employs MobileNetV3 as a backbone to lightweight the proposed framework. In addition, the framework uses DeepSORT of object tracking algorithm to interpolate frames not predicted by the model. The post-processing algorithm in our framework classifies the correlation between workers and PPE into four statuses based on the results predicted by YOLACT and the interpolated results from DeepSORT. The results showed that the fine-tuned model achieved 66.4 mean average precision50, and the algorithm successfully determined workers’ PPE-wearing status detection with 91.3% accuracy. This study shows the potential to prevent occupational injuries and reduce social costs by automating monitoring at construction sites in real-time.
Influence in investor-state dispute settlement: a dynamic concept
Authors: Cahill-O’Callaghan Rachel , Howard Anna , Brekoulakis Stavros
Published: March 2023

Investor-state dispute settlement (ISDS) plays an increasingly important role in international trade resolution. The decisions have significant financial and in many cases policy implications, yet little is known about the formation of the ad-hoc panels and the decision-making process. Drawing on empirical evidence from interviews with key actors in the ISDS system, this article argues that influence plays a central role in both processes. The analysis further develops the framework for understanding influence in international decision-making to accommodate external factors (those visible to those appointing the decision-makers) and internal factors (those factors that become visible in the decision-making room). It draws our attention to the nuanced relationship and distinction between the characterization of influence in both contexts and poses a challenge to the traditional focus of appointments based on power and prestige which neglects the group decision-making context and the multifaceted construction of influence in this increasingly important method of adjudication.
Intralobar pulmonary sequestration: robotical resection using indocyanine green
Authors: Mohnke Jonas , Housmanou Danjouma Cheufou
Published: March 2023

Pulmonary sequestration (PS) is a relatively rare congenital lung anomaly. There are two different subtypes of PS, intralobar and extralobar sequestration. The majority of cases is constituted by intralobar sequestration. Here, we report a case of a 39-year-old female with intralobar sequestration, which was successfully resected by robotic-assisted surgery.
A search for chemical anomalies of seven A-type stars
Authors: Nasolo Yahya , Çalışkan Seyma
Published: March 2023

We present a chemical abundance analysis of seven A-type stars with no detailed chemical abundance measurements in the literature. High-resolution spectra of the targets – HD 2924, HD 4321, HD 26553, HD 125658, HD 137928, HD 154713, and HD 159834 – were obtained using the Coudé Echelle Spectrograph at the TÜBİTAK National Observatory. We determined the atmospheric abundances of the samples and measured the elemental abundances of C, N, O, Na, Mg, Al, Si, S, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Y, Zr, Ba, La, Ce, Nd, Sm, Eu, and Gd. The masses of the stars were estimated based on their evolutionary tracks, and their ages were calculated using isochrones. We also calculated the radii of the stars. The abundance patterns of HD 4321, HD 125658, and HD 154713 were found to be in agreement with those of classical Am stars, with underabundant Ca and Sc, overabundant heavier elements, and moderate overabundance of iron-peak elements. We found that HD 137928 and HD 159834 have abundance characteristics similar to marginal Am-type stars. The elemental distributions of HD 2924 and HD 26553 are consistent with the pattern of normal A-type stars. The iron, nickel, and zinc abundances of HD 125658 and HD 137928 are significantly higher than those of other Am stars. These values suggest that they are among the most metal-rich Am stars.
Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility
Authors: Li Ren-Yan , Yang Dan , He Yan-Ji , Zhou Yong , Li Cheng-Cheng , Li Lian-Bing , Liao Ming-Xing , Deng Zhong-Liang , Zhao Le-Tian , Zhang Tian-Feng , Luo Yong , Wang Ying-Xiong , Gao Yan-Fei
Published: March 2023

DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.
Hello darkness, my old friend: 3-KETOACYL-COENZYME A SYNTHASE4 is a branch point in the regulation of triacylglycerol synthesis in Arabidopsis thaliana
Authors: Luzarowska Urszula , Ruß Anne-Kathrin , Joubès Jérôme , Batsale Marguerite , Szymański Jędrzej , P. Thirumalaikumar Venkatesh , Luzarowski Marcin , Wu Si , Zhu Feng , Endres Niklas , Khedhayir Sarah , Schumacher Julia , Jasinska Weronika , Xu Ke , Correa Cordoba Sandra Marcela , Weil Simy , Skirycz Aleksandra , Fernie Alisdair Robert , Li-Beisson Yonghua , Fusari Corina M , Brotman Yariv
Published: March 2023

Plant lipids are important as alternative sources of carbon and energy when sugars or starch are limited. Here, we applied combined heat and darkness or extended darkness to a panel of ∼300 Arabidopsis (Arabidopsis thaliana) accessions to study lipid remodeling under carbon starvation. Natural allelic variation at 3-KETOACYL-COENZYME A SYNTHASE4 (KCS4), a gene encoding an enzyme involved in very long chain fatty acid (VLCFA) synthesis, underlies the differential accumulation of polyunsaturated triacylglycerols (puTAGs) under stress. Ectopic expression of KCS4 in yeast and plants proved that KCS4 is a functional enzyme localized in the endoplasmic reticulum with specificity for C22 and C24 saturated acyl-CoA. Allelic mutants and transient overexpression in planta revealed the differential role of KCS4 alleles in VLCFA synthesis and leaf wax coverage, puTAG accumulation, and biomass. Moreover, the region harboring KCS4 is under high selective pressure and allelic variation at KCS4 correlates with environmental parameters from the locales of Arabidopsis accessions. Our results provide evidence that KCS4 plays a decisive role in the subsequent fate of fatty acids released from chloroplast membrane lipids under carbon starvation. This work sheds light on both plant response mechanisms and the evolutionary events shaping the lipidome under carbon starvation.
The maize ZmVPS23-like protein relocates the nucleotide-binding leucine-rich repeat protein Rp1-D21 to endosomes and suppresses the defense response
Authors: Sun Yang , Ma Shijun , Liu Xiangguo , Wang Guan-Feng
Published: March 2023

Plants often utilize nucleotide-binding leucine-rich repeat (NLR) proteins to perceive pathogen infections and trigger a hypersensitive response (HR). The endosomal sorting complex required for transport (ESCRT) machinery is a conserved multisubunit complex that is essential for the biogenesis of multivesicular bodies and cargo protein sorting. VPS23 is a key component of ESCRT-I and plays important roles in plant development and abiotic stresses. ZmVPS23L, a homolog of VPS23-like in maize (Zea mays), was previously identified as a candidate gene in modulating HR mediated by the autoactive NLR protein Rp1-D21 in different maize populations. Here, we demonstrate that ZmVPS23L suppresses Rp1-D21-mediated HR in maize and Nicotiana benthamiana. Variation in the suppressive effect of HR by different ZmVPS23L alleles was correlated with variation in their expression levels. ZmVPS23 also suppressed Rp1-D21-mediated HR. ZmVPS23L and ZmVPS23 predominantly localized to endosomes, and they physically interacted with the coiled-coil domain of Rp1-D21 and mediated the relocation of Rp1-D21 from the nucleo-cytoplasm to endosomes. In summary, we demonstrate that ZmVPS23L and ZmVPS23 are negative regulators of Rp1-D21-mediated HR, likely by sequestrating Rp1-D21 in endosomes via physical interaction. Our findings reveal the role of ESCRT components in controlling plant NLR-mediated defense responses.
Phosphorylation and ubiquitination of OsWRKY31 are integral to OsMKK10-2-mediated defense responses in rice
Authors: Wang Shuai , Han Shuying , Zhou Xiangui , Zhao Changjiang , Guo Lina , Zhang Junqi , Liu Fei , Huo Qixin , Zhao Wensheng , Guo Zejian , Chen Xujun
Published: March 2023

Mitogen-activated protein kinase (MPK) cascades play vital roles in plant innate immunity, growth, and development. Here, we report that the rice (Oryza sativa) transcription factor gene OsWRKY31 is a key component in a MPK signaling pathway involved in plant disease resistance in rice. We found that the activation of OsMKK10-2 enhances resistance against the rice blast pathogen Magnaporthe oryzae and suppresses growth through an increase in jasmonic acid and salicylic acid accumulation and a decrease of indole-3-acetic acid levels. Knockout of OsWRKY31 compromises the defense responses mediated by OsMKK10-2. OsMKK10-2 and OsWRKY31 physically interact, and OsWRKY31 is phosphorylated by OsMPK3, OsMPK4, and OsMPK6. Phosphomimetic OsWRKY31 has elevated DNA-binding activity and confers enhanced resistance to M. oryzae. In addition, OsWRKY31 stability is regulated by phosphorylation and ubiquitination via RING-finger E3 ubiquitin ligases interacting with WRKY 1 (OsREIW1). Taken together, our findings indicate that modification of OsWRKY31 by phosphorylation and ubiquitination functions in the OsMKK10-2-mediated defense signaling pathway.
Taking Cover: Human Capital Accumulation in the Presence of Shocks and Health Insurance
Authors: Font-Gilabert Paulino
Published: March 2023

Using the expansion of a large-scale health-insurance program in Mexico and variation in local rainfall levels, this study explores whether the program-induced increase in healthcare coverage protected the cognitive attainment of primary school children in the event of adverse rainfall shocks. Results show that the universalization of healthcare mitigated the negative effect of atypical rainfall on test scores, particularly in more marginalized and rural areas. An analysis of the mechanisms at play shows a reduced incidence of sickness among children, lower demand for their time, and higher stability in household consumption among program-eligible families exposed to rainfall shocks.
Fossil diversity in ‘dawn’ hexapods (Diplura: Projapygoidea), with direct evidence for being chemically predaceous in the Cretaceous
Authors: Sánchez-García Alba , Sendra Alberto , Davis Steven , Grimaldi David A
Published: March 2023

Diplurans are among the earliest hexapods in the geological record. These primitively wingless relatives of insects are infrequently encountered despite being pervasive in soil habitats. Two groups have disparate adaptations for hunting, one mechanical and the other chemical, in Japygoidea and Projapygoidea, respectively. Here, we report three genera (two new) and four species of fossil Projapygidae preserved in Mesozoic and Cenozoic ambers: Electroprojapyx alchemicus gen. et sp. nov. in mid-Cretaceous Myanmar amber, and Symphylurinopsis punctatus gen. et sp. nov. and two species (unnamed) of Symphylurinus in Miocene Dominican amber. The exceptionally preserved specimens possess cerci that are morphologically specialized for expelling a glandular substance on prey. The new Cretaceous E. alchemicus is a stem group to all living species of the family and provides conclusive Mesozoic evidence for a rare type of predation involving offensive (vs. defensive) secretions. The specimen was fossilized in a preying-and-spraying position with its presumptive meal, a Symphypleona springtail (Collembola), reflecting the behavioural predatory repertoire of modern relatives. Apart from one Cenozoic species, these rare specimens represent the only fossil record of the family Projapygidae. Our findings demonstrate that these basal hexapods were predators of small arthropods of ancient forest soils and enrich our understanding of palaeoecological associations and behavioural strategies paramount for the survival of species.
Severe Smallness as Predictor of Adverse Perinatal Outcome in Suspected Late Small-for-Gestational-Age Fetuses: Systematic Review and Meta-analysis
Authors: Meler E. , Martinez-Portilla R. J. , Caradeux J. , Mazarico E. , Gil-Armas C. , Boada D. , Martinez J. , Carrillo P. , Camacho M. , Figueras F.
Published: March 2023

Various adverse perinatal outcomes, such as neonatal morbidity, fetal death, suboptimal neurodevelopment, and delayed effects as an adolescent and adult, are associated with fetal growth restriction (FGR). Failure to detect this condition prenatally is recognized as a contributor to avoidable perinatal death. This systematic review and meta-analysis assessed the evidence regarding the use of severe smallness (eg, birth weight <3%ile) for prediction of adverse perinatal outcome in fetuses with suspected late-onset small for gestational age (SGA) birth.

Study eligibility included third-trimester singleton pregnancies with suspected SGA fetuses, based on an estimated fetal weight (EFW) or abdominal circumference <10th percentile, diagnosed at or after 32 weeks' gestation. Included studies were both retrospective cohort studies and randomized controlled trials and reported on the following outcomes: (1) admission to the neonatal intensive care unit (NICU); (2) neonatal acidosis; (3) cesarean delivery for intrapartum fetal compromise; (4) Apgar score <7 at 5 minutes; (5) perinatal death (including stillbirth and neonatal death within 48 hours after birth); and (6) composite adverse perinatal outcome. The analysis identified a total of 6541 articles via database search, and 1 additional study was identified manually. A final review resulted in the inclusion of 12 cohort studies.

The studies included 3639 fetuses with suspected late-onset SGA, of which 1246 had severe SGA <3%ile. Significant associations were found between suspected severe SGA and the composite adverse perinatal outcome, with an odds ratio (OR) of 1.97 (95% confidence interval [CI], 1.33–2.92), NICU admission (OR, 2.87; 95% CI, 1.84–4.47), and perinatal death (OR, 4.26; 95% CI, 1.07–16.93). However, the analysis found limited performance of suspected severe SGA to predict perinatal outcomes, with an area under the curve of 60.9% for the composite adverse perinatal outcome. The meta-analysis results indicate that the performance of severe SGA in the study was poorer than that reported for uterine artery Doppler and cerebroplacental ratio. The current analysis found a positive and negative likelihood ratio of 1.53 and 0.76, respectively, for composite adverse perinatal outcome associated with severe smallness.

Despite its association with a higher risk of perinatal complications, suspected severe SGA failed to perform as a standalone parameter for the prediction of adverse perinatal outcome.
Evidence-Based Approaches to Labor Induction
Authors: Saucedo Alexander M. , Cahill Alison G.
Published: March 2023

Importance

The induction rate continues to increase in the United States placing pressure on the health care system with increasing cost and time spent on labor and delivery. Most labor induction regimens have evaluated uncomplicated singleton-term gestations. Unfortunately, the optimal labor regimens of medically complicated pregnancies have not been well described.

Objective

The aim of this study was to review the current available evidence regarding the various labor induction regimens and understand the evidence that exists for induction regimens in complicated pregnancies.

Evidence Acquisition

Data were acquired by a literature search on PubMed, ClinicalTrials.gov, the Cochrane Review database, the most recent American College of Obstetricians and Gynecologists practice bulletin on labor induction, and a review of the most recent edition on widely used obstetric texts for key words related to labor induction.

Results

Many heterogeneous clinical trials exist examining various labor induction regimens such as prostaglandin only, oxytocin only, or a combination of mechanical dilation with prostaglandins or oxytocin. Several Cochrane systematic reviews have been performed, which suggest a combination of prostaglandins and mechanical dilation results in an improved time to delivery when compared with single-use methods. Evaluating pregnancies complicated by maternal or fetal conditions, there exist retrospective cohorts describing significantly different labor outcomes. Although a few of these populations have planned or active clinical trials, most do not have an optimal labor induction regimen described.

Conclusions and Relevance

Most induction trials are significantly heterogeneous and limited to uncomplicated pregnancies. A combination of prostaglandins and mechanical dilation may result in improved outcomes. Complicated pregnancies have significantly different labor outcomes; however, almost none have well-described labor induction regimens.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this activity, the learner should be better able to describe the various inpatient cervical ripening regimens available in the United States; discuss the evidence on the current inpatient cervical ripening regimens available for several maternal medical conditions (obesity, hypertensive disorders of pregnancy, advanced maternal age, and others); and explain current inpatient cervical ripening regimens available for several fetal medical conditions (preterm gestations, fetal growth restriction, and others).
Plasma neurofilament light levels show elevation prior to diagnosis of sporadic motor neuron disease in the UK Biobank cohort
Authors: Smith Erin N. , Lee Jonghun , Prilutsky Daria , Zicha Stephen , Wang Zemin , Han Steve , Zach Neta
Published: March 2023

Objective

Motor neuron disease (MND) is a debilitating neurodegenerative disease with profound unmet need. In pre-symptomatic mutation carriers, elevations in neurofilament light (NfL) precede symptom onset, however, the presence and timing of elevation is much more difficult to study in sporadic cases.

Methods

Using the UK Biobank cohort, we tested whether plasma NfL predicted risk of diagnosis of sporadic MND using survival analysis.

Results

We identified 241 MND patients with pre-diagnosis NfL data, of which 203 (84%) lacked predicted loss of function or deleterious missense variants in established ALS genes. A total of 42,752 controls without MND were obtained from a random sample of UK Biobank participants. At two years pre-diagnosis, we found that NfL levels in patients exceeded the 95thpercentile of controls and that patients could be discriminated from controls at high accuracy (AUC = 0.95 (95% CI 0.89-1.01)). In participants with hospital record follow-up after study enrollment, a 2-fold increase in NfL levels was associated with a 3.4 fold risk of receiving an MND diagnosis per year (95% CI 2.9-3.9, P = 4 × 10−64)).

Discussion

Our findings show that NfL can identify sporadic MND as early as 2 years prior to diagnosis.
Respiration-Triggered Olfactory Stimulation Reduces Obstructive Sleep Apnea Severity – A Prospective Pilot Study
Authors: Perl Ofer , Kemer Lilach , Green Amit , Arish Nissim , Corcos Yael , Arzi Anat , Dagan Yaron
Published: March 2023

Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing condition characterized by repetitive reduction in breathing during sleep. Current care standard for OSA is continuous positive air pressure devices, often suffering from low tolerance due to limited adherence. Capitalizing on the unique neurocircuitry of olfactory perception and its retained function during sleep, we conducted a pilot study to test transient, respiration-based olfactory stimulation as a treatment for OSA markers. Thirty-two OSA patients (Apnea-Hypopnea Index (AHI)≥15 events/hour) underwent two polysomnography sessions, ‘Odor’ and ‘Control’, in random order. In ‘Odor’ nights, patients were presented with transient respiratory-based olfactory stimulation delivered via a computer-controlled commercial olfactometer (Scentific). The olfactometer, equipped with a wireless monitoring, analyzed respiratory patterns and presented odor upon detection of respiratory events. No odors were presented in ‘Control’ nights. Following exclusions, 17 patients entered analysis (4 women, 47.4 (10.5) years, BMI: 33.8 (7.8)). We observed that olfactory stimulation during sleep reduced AHI (‘Odor’:17.2 (20.9), ‘Control’: 28.2 (18.6), z=- 3.337, p=0.000846, BF10=57.9), reflecting an average decrease of 31.3% in event number. Relatedly, stimulation reduced the oxygen desaturation index (ODI) by 26.9% (‘Odor’: 12.5 (15.8), ‘Control’: 25.7 (25.9), z=-3.337, p=0.000846, BF10=9.522. This effect was not linked to baseline OSA markers severity (ρ=-0.042, p=0.87). Olfactory stimulation did not arouse from sleep or affect sleep structure, measured as time per sleep stage (F(1,16)=0.088, p=0.77). In conclusion, olfactory stimulation during sleep was effective in reducing OSA markers severity without inducing arousals and may provide a novel treatment for OSA, prompting continued research.
PRL1 negatively regulates Rho GTPase-independent and - dependent signaling pathways maintaining actin microfilament dynamic for pavement cell morphogenesis
Authors: Gao Xiaowei , Yang Bo , Zhang Jingjing , Wang Chi , Ren Huibo , Fu Ying , Yang Zhenbiao
Published: March 2023

Actin dynamic is critical for cell morphogenesis in plants, but the signaling mechanisms underlying its regulation are not well understood. Here we foundPRL1(PleiotropicRegulatoryLocus1) modulates leaf pavement cell (PC) morphogenesis in Arabidopsis by maintaining the dynamic homeostasis of actin microfilaments (MF). Our previous studies indicated PC shape formation was mediated by the counteracting ROP2 and ROP6 signaling pathways that promote the organization of cortical MF and microtubules (MT), respectively. Our genetic screen forROP6enhancers identifiedprl1alleles. Genetic analysis suggested thatprl1acted synergistically withROP2andROP6in regulation of PC morphogenesis. We further found that the activities of ROP2 and ROP6 were increased and decreased inprl1mutants, respectively. Interestinglyprl1was found to prefer to depolymerize MF independent of ROP2 and ROP6. Stress (high salinity and low temperature) induced similar changes of ROP activities as doprl1mutations. Together our findings provided evidence that PRL1 governed two signaling pathways that counteractively maintain actin dynamics and resultant cell morphogenesis.