bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiologie von Ängsten und Sorgen
Authors: Jacobi Frank , Marchewka Juliette
Published: August 2022

Angst und Sorge werden klinisch relevant, wenn sie nicht mehr funktional sind – etwa wenn sie überschießend stark sind (Panikattacken), wenn sie nicht angemessen mit realen Gefahren assoziiert sind (Phobien) oder wenn sie im Zuge starken Vermeidungsverhaltens zu Behinderungen und Teilhabe-Beeinträchtigungen führen. Wir berichten von Häufigkeit und Verbreitung von Angststörungen sowie normalen bzw. sub-klinischen Ängsten und Sorgen.
COVID-19 – auch eine Pandemie der Angst
Authors: Teufel Martin , Dinse Hannah , Skoda Eva-Maria
Published: August 2022

Die Coronapandemie hält die Welt seit 2019 in Atem. Nie erahnter Kontrollverlust erfasste die Menschheit. Eine Auseinandersetzung mit dem unbekannten Virus war kaum möglich, da zunächst Wissen zu Ausbreitung, Gefährlichkeit und Schutzmöglichkeiten fehlten. Furcht vor dem Virus verwandelte sich zu generalisierter Angst. Erst nach und nach kam individuelle und gesellschaftliche Selbstwirksamkeit zurück – parallel zu einem Habituationsprozess.
Die Polizei – stets Dein Freund und Helfer?
Authors: Bossenmayer Jörg
Published: August 2022

„Wo gehobelt wird, da fallen Späne“ – diese Volksweisheit gilt auch bezüglich der beruflichen Tätigkeit von Therapeut*innen. Auch sie sind nicht davor gefeit, sich bei ihrer Arbeit strafbar zu machen.
Überarbeitete S3-Leitlinie: Behandlung von Angststörungen
Authors: Beutel Manfred E. , Wiltink Jörg , Werner Antonia M. , Bandelow Borwin
Published: August 2022

Seit 2019 hat eine Leitliniengruppe mit 35 Expert*innen die 2014 erschienenen deutschen Leitlinien zur Behandlung von Angststörungen überarbeitet 1, 2, 3. Vertreten waren insgesamt 29 deutsche Fachgesellschaften und Berufsverbände sowie Patientenselbsthilfeorganisationen. Dieser Beitrag fasst die wichtigsten Empfehlungen sowie die Neuerungen der überarbeiteten Leitlinie zusammen.
Präventive Kontrolle im Vier-Augen-Prinzip
Authors: Kapps Julia , Krukenkamp Sabine
Published: August 2022

Wer zählt was, wann und wie bei einer Operation und dokumentiert die Ergebnisse? Was ist bei unstimmigen oder fehlerhaften Zählkontrollen zu tun? Und wie geht das OP-Team mit einem vermuteten oder tatsächlichen Schadensfall um? Antworten liefert unser CNE Schwerpunkt.
Die Kraft der Beobachtung
Authors: Singer Dominique
Published: August 2022

Liebe Leserinnen und Leser

vielen in der Neonatologie erfahrenen Pflegekräften und Ärzt:innen
ist der Umstand geläufig, dass man gefährdeten Früh- und
Neugeborenen an ihrem Bewegungsmuster „irgendwie“ ansieht, wenn sie
später eine motorische Beeinträchtigung entwickeln. Das ist deswegen
bemerkenswert, weil die Motorik bei Neugeborenen und jungen Säuglingen noch
nicht unter zentraler Kontrolle steht und eine spastische Zerebralparese daher
für gewöhnlich erst dann erkennbar wird, wenn die Myelinisierung der
Pyramidenbahn so weit fortgeschritten ist, dass sich auch deren Schädigung
entsprechend auswirkt. Es ist das Verdienst des österreichischen
Entwicklungsneurologen Heinz Friedrich Rudolf Prechtl (1927–2014), der im
niederländischen Groningen lehrte, dass er das frühkindliche
Bewegungsmuster einer systematischen Auswertung zugänglich gemacht hat, die
auch valide diagnostische und prognostische Aussagen erlaubt.
Telemedicine Health Care Delivery: A Global Strategy during COVID-19 Pandemic and Its Optimisation for Homoeopathy in India
Authors: Manchanda Raj Kumar , Ponnam Hima Bindu , Rompicherla Kiranmayee G.R. , Nayak C
Published: August 2022

Background After the declaration of COVID-19 as a pandemic by the World Health Organisation, the physical medical consultations became almost impossible. Telemedicine (TM) health care delivery (HCD) seemed to be the only means to handle the crisis and served as a boon in the management of mild to moderate COVID-19 cases. The telemedicine practice (TMP) spread worldwide in no time, and the same was adopted even in homoeopathic consultations.

Objective The aim of this study is to highlight the TM practice globally and its adoption in homoeopathy concerning notified guidelines by the Central Council of Homoeopathy, erstwhile National Commission for Homoeopathy, Ministry of AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Sow-Rigpa, Siddha and Homoeopathy), Government of India.

Conclusion TMP has become a necessity for easy access to essential and universal health care and to treat remotely located patients. The publication of these guidelines for homoeopathic consultations is timely to strengthen and encourage its usage in public HCD. There is a need to periodically evaluate its optimal integration in digital health care in the future.
Systematic Review and Meta-analysis of Peripheral Blood DNA Methylation Studies in Inflammatory Bowel Disease
Authors: Joustra Vincent , Hageman Ishtu L , Satsangi Jack , Adams Alex , Ventham Nicholas T , de Jonge Wouter J , Henneman Peter , D’Haens Geert R , Li Yim Andrew Y F
Published: August 2022

Background and Aims

Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease [IBD] patients. However, a comprehensive summary and meta-analysis of peripheral blood leukocyte [PBL] DNA methylation studies has thus far not been conducted. Here, we systematically reviewed all available literature up to February 2022 and summarized the observations by means of meta-analysis.

Methods

We conducted a systematic search and critical appraisal of IBD-associated DNA methylation studies in PBL using the biomarker-based cross-sectional studies [BIOCROSS] tool. Subsequently, we performed meta-analyses on the summary statistics obtained from epigenome-wide association studies [EWAS] that included patients with Crohn’s disease [CD], ulcerative colitis [UC] and/or healthy controls [HC].

Results

Altogether, we included 15 studies for systematic review. Critical appraisal revealed large methodological and outcome heterogeneity between studies. Summary statistics were obtained from four studies based on a cumulative 552 samples [177 CD, 132 UC and 243 HC]. Consistent differential methylation was identified for 256 differentially methylated probes [DMPs; Bonferroni-adjusted p ≤ 0.05] when comparing CD with HC and 103 when comparing UC with HC. Comparing IBD [CD + UC] with HC resulted in 224 DMPs. Importantly, several of the previously identified DMPs, such as VMP1/TMEM49/MIR21 and RPS6KA2, were consistently differentially methylated across all studies.

Conclusion

Methodological homogenization of IBD epigenetic studies is needed to allow for easier aggregation and independent validation. Nonetheless, we were able to confirm previous observations. Our results can serve as the basis for future IBD epigenetic biomarker research in PBL.
The quality of reporting in cardiac MRI artificial intelligence segmentation studies - a systematic review
Authors: Alabed S , Maiter A , Mahmood A , Daniel S , Salehi M , Jenkins S , Sharkey M , Rakocevic V , Dwivedi K , Asaadi H , Mamalakis M , O'regan D P , Garg P , Van Der Geest R , Swift A J
Published: August 2022

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by an NIHR AI Award, AI_AWARD01706. This research was also funded in part, by the Wellcome Trust [Grant number 205188/Z/16/Z ].

Background

There has been a rapid increase in the number of Artificial Intelligence (AI) studies of cardiac MRI (CMR) segmentation. AI has huge potential to improve image analysis assessments. However, advancement and clinical translation in this field depend on researchers presenting their work in a transparent and reproducible manner.

Purpose

This systematic review aimed to evaluate the quality of reporting in AI studies involving CMR segmentation.

Methods

MEDLINE and EMBASE databases were searched for AI CMR segmentation studies on 18/11/2021. The flow of study inclusion is shown in Figure 1. Any AI method to segment any cardiac structure on CMR was eligible for inclusion. Each study was assessed for compliance with the Checklist for Artificial Intelligence in Medical Imaging (CLAIM).

Results

70 studies were included in the qualitative analysis. Studies were published between 2015 to 2021, with the majority (71%) published in 2020 and 2021. Most studies were performed in Europe (33%), China (27%) and the USA (26%). Short-axis sections were segmented in 70% of studies and most commonly included both ventricles (51%) or the left ventricle alone (30%). 20 different architecture implementations were represented. Figure 2 summarises the most relevant CLAIM domains to AI segmentation. The training sample eligibility criteria, demographics and clinical characteristics were not reported in 47% and 81% of studies, respectively. Ground truth annotations, source of the annotations and annotation tool were absent in 31%, 36% and 51% of studies respectively. Preprocessing steps and software libraries and packages used in training were not included in 27% and 24%. Details on the training approach including the number of models trained and method of selecting the final model were missing in 20% and 17% of the studies. Methods of validation or testing on external data, inter- and intra- rater variability and failure analysis were unreported in 57%, 63% and 74%, respectively.

Conclusion

This systematic review highlights important gaps in the AI literature of CMR studies. We identified key items missing in the dataset description, model development, validation and testing that limit the transparency, reproducibility and hence validity of published AI studies. This review may support closer adherence to established frameworks for reporting standards.
Artificial intelligence with spatial-attention for ventricular volumes and mass assessment in cardiac magnetic resonance images with susceptibility artifacts
Authors: Penso M , Babbaro M , Guglielmo M , Moccia S , Giacari G M , Chiesa M , Maragna R , Rabbat M G , Pepi M , Pontone G
Published: August 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

Segmentation of cardiac magnetic resonance (CMR) images is an essential step for evaluating dimensional and functional ventricular parameters but may limited by noise artefacts, such as the increasing diffusion of implantable devices causing distortion of the magnetic field.

Purpose

The aim of this paper is to investigate the accuracy of a deep learning (DL) approach for automatic segmentation of cardiac structures from CMR images characterized by magnetic susceptibility artifact images.

Methods

A retrospective database of SAX (short axis) cine CMR images obtained from 216 patients using a 1.5 Tesla scanner was used to develop and validate the proposed DL approach, subdividing patients into two subgroups, considering the presence (n=86) or absence (n=130) of a cardiac implantable electronic device. A novel convolutional neural network (CNN) was proposed to extract the left (LV) and right (RV) ventricle endocardium and left ventricle epicardium (LV mass). The proposed network takes advantage from a spatial attention module which introduces an adaptive feature refinement through a spatial weighting strategy to identify salient image regions even in the presence of artifacts. To improve segmentation, especially for images with artifacts, a compounded loss function is introduced. Segmentation results were assessed against manual tracings and commercial CMR analysis software.

Results

Results of correlation and Bland-Altman analyses on images with artifacts were reported for the proposed CNN and the commercial software (CS) in respect to the manual gold standard (GT). Also interobserver variability between O1 and O2 was tested. The proposed method reached higher segmentation accuracy than CS, with performance comparable to expert inter-observer variability (Picture 1). It is possible to appreciate how all the contours were properly depicted using the proposed CNN, with results comparable to the manual tracings. On the opposite, the CS resulted in imprecise segmentations of LV and RV endocardium and LV epicardium in presence of susceptibility artefacts caused by cardiac implantable electronic device affecting images' quality (Picture 2). Furthermore, the automatic approach was at least 100 times faster than manual segmentation in providing cardiac parameters.

Conclusion

The proposed method reached promising performance in cardiac segmentation from CMR images with susceptibility artifacts and alleviates time consuming expert physician contourn segmentation.
Enlightenment and reform in the French Atlantic empire: Véron de Forbonnais, Pierre-Louis de Saintard, and the 1756 debate over the admission of neutral commerce in the Antillean colonies
Authors: Talini Giulio
Published: August 2022

This article analyses the political and intellectual debates that took place in the French Empire concerning the admission of neutral commerce to the colonies at the outbreak of the Seven Years’ War (1756–1763). The decision taken by the Minister for the Navy, Machault d’Arnouville, was justified as the only means available to provide the Antilles with essential goods in the face of British naval primacy. Nonetheless, it met with strenuous opposition from the French chambres de commerce, which were reluctant to redistribute power in favour of the colonies. On the other hand, the economist Véron de Forbonnais and the Dominguan planter Pierre-Louis de Saintard strongly supported the minister, albeit for different reasons and goals. Linking questions of colonial dependence and neutrality, their theories disclose new perspectives on the political and intellectual impact of enlightened reform in the French Atlantic empire.
Vaccination Against Measles, Mumps, Rubella and Incident Inflammatory Bowel Disease in a National Cohort of Privately Insured Children
Authors: Kim Catherine , Yin Zhe , Kamdar Neil , Stidham Ryan
Published: August 2022

Background

Infection is believed to be a potential trigger for inflammatory bowel disease (IBD). Whether vaccination against childhood infections including measles, mumps, and rubella may reduce risk of IBD is uncertain.

Methods

We conducted a retrospective cohort study using de-identified claims data from a national private payer (Optum Clinformatics Data Mart). Eligible infants were born between 2001 and 2018 and were continuously enrolled with medical and pharmacy coverage from birth for at least 2 years (n = 1 365 447). Measles, mumps, and rubella vaccination or MMR is administered beginning at 12 months of age. Cox proportional hazard regression models were used to compare time with incident disease in children by category of vaccination, after adjustment for sex, birth year, region of country, history of allergy to vaccines, and seizure history.

Results

The incidence of early pediatric IBD increased between 2001 and 2018. Ten percent (n = 141 230) of infants did not receive MMR, and 90% (n = 1 224 125) received at least 1 dose of MMR. There were 334 cases of IBD, 219 cases of Crohn’s disease, and 164 cases of ulcerative colitis. Children who had received at least 1 dose of MMR had lower risk for IBD than children who did not (hazard ratio, 0.71; 95% confidence interval, 0.59-0.85). These associations did not change after further adjustment for childhood comorbid conditions, preterm birth, or older siblings affected with IBD. Similar associations were observed for MMR with Crohn’s disease and ulcerative colitis, although these did not reach statistical significance.

Conclusion

MMR is associated with decreased risk for childhood IBD.
Effects of xylanase on growth performance, nutrient digestibility, serum metabolites, and fecal microbiota in growing pigs fed wheat–soybean meal-based diets
Authors: Cheng Hao , Li Zhiqing , Zhang Fan , Liu Shanghang , Jiang Qian , Chen Jiashun , Tan Bie , Fan Zhiyong , Ma Xiaokang
Published: August 2022

This experiment investigated the effects of xylanase on growth performance, nutrient digestibility, serum metabolites, and fecal microbiota in growing pigs fed wheat–soybean meal-based diets. Seventy-two crossbred pigs (Duroc × [Landrace × Large White]) pigs (body weight of 23.30 ± 1.51 kg) were allotted two treatments with six pens per treatment and six pigs per pen. The diets were a wheat–soybean meal-based diet (Control group) and a wheat–soybean meal-based diet supplemented with 500 U/kg xylanases (XYL group). The experiment was divided into two periods (phase 1: days 1 to 35 and phase 2: days 36 to 70). Xylanase improved G:F during phase 1 and the entire experiment (P < 0.05) and tended to improve G:F during phase 2 (P = 0.09). Compared with the control group, pigs in the XYL group had greater apparent total tract digestibility of dry matter, organic matter, and gross energy on days 35 and 70 (P < 0.05) and had greater apparent ileal digestibility of amino acids (histidine, lysine, methionine, and serine) on day 70 (P < 0.05). The fecal microbiota in the XYL group contained greater abundances of g_Terrisporobacter, g_Lactobacillus, g_Clostridium_sensu_stricto_1, and g_Romboutsia than the Control group on day 70. Xylanase increased the fecal Lactobacillus populations on day 35 (P < 0.05). On days 35 and 70, xylanase reduced the fecal E. coli populations (P < 0.05). Supplementing xylanase to wheat–soybean meal-based diets collectively improved fecal microbiota, and nutrient digestibility, thereby improving growth performance in growing pigs.
First-order logic of change
Authors: Świętorzecka Kordula
Published: August 2022

We present the first-order logic of change, which is an extension of the propositional logic of change $\textsf {LC}\Box $ developed and axiomatized by Świętorzecka and Czermak (2015, Log. et Anal., 232, 511–527). $\textsf {LC}\Box $ has two primitive operators: ${\mathcal {C}}$ to be read it changes whether and $\Box $ for constant unchangeability. It implements the philosophically grounded idea that with the help of the primary concept of change it is possible to define the concept of time. One of the characteristic axioms for ${\mathcal {C}}$ is ${\mathcal {C}} A \to {\mathcal {C}}\neg A$ and one of the primitive rules is $\omega $-rule introducing $\Box $. It turns out that the next operator is definable in $\textsf {LC}\Box $. Logic $\textsf {LC}\Box $ with next is equivalent to certain fragment of $\textsf {LTL}$ extended by the appropriate definition of ${\mathcal {C}}$. Recently, $\textsf {LC}\Box $ has also been modified to the propositional logic of ‘branching’ changes $\textsf {BTC}$ by Łyczak (2022, Log. J. IGPL) and the logic of ‘parallel’ changes $\textsf {LC}\Box $ ↳ by Świętorzecka and Łyczak (2022, Log. Log. Philios.). Extended in an appropriate manner, $\textsf {BTC}$ is equivalent to a certain fragment of logic $\textsf {CTL}$ to which definitions of two kinds of changes have been added. Here we propose an extension of $\textsf {LC}\Box $ to first-order logic in which, again, the only primitive modal operators are ${\mathcal {C}}$ and $\Box $. We interpret our logic in the semantics of histories of changes. We give an axiomatic system $\textsf {LC}\Box Q$ for the considered logic, and we show selected theses about some relationships between ${\mathcal {C}}$, $\Box $ and $\forall $ (in particular, we prove two versions of the Barcan formula). Then we prove the completeness of $\textsf {LC}\Box Q$. Finally, we compare our logic with $\textsf {FOLT}$ and show the relation between $\textsf {LC}\Box Q$ and a certain fragment of the Kröger system $\varSigma $ to which the definition of ${\mathcal {C}}$ was added.
Diversifying the Field of Forestry Through a Graduate Fellowship Program: A Pilot Study on the Expectations of Students of Color
Authors: Arenas Aaron A , Spence Porché L , Nilon Charles H , Leggett Zakiya H
Published: August 2022

Overall interest and involvement in forestry is relatively low for students of color compared to other STEM programs. This exploratory study aims to further understand the reasons graduate students of color in a National Needs Fellowship (NNF) program decide to pursue a career in forestry. Initial survey data showed that graduate students of color are motivated by pursuing specific forestry topics in the field while also having differing expectations with regard to career and financial opportunities. The results of this study could provide ideas on opportunities NNF-funded and other programs can take to further support diversity in the field of forestry; however, more research is needed.

Study Implications

Given the results of this pilot study, it is important to note that students of color who accept a graduate fellowship do so with goals of exploring a particular interest in the field of forestry. An assumption also exists that their degrees and experiences in certain graduate fellowship programs will yield long-term benefits, such as employment opportunities and high salaries. However, additional information would be helpful in strengthening the results of this study, which could include increasing the number of participants for more quantitative data or collecting qualitative data to gather additional details and information on the survey responses.
Surgical treatment for kyphotic deformity after anterior cervical fusion with a severely tortuous vertebral artery: a case report
Authors: Noguchi Hiroshi , Koda Masao , Funayama Toru , Takahashi Hiroshi , Miura Kousei , Eto Fumihiko , Shibao Yosuke , Sato Kosuke , Asada Tomoyuki , Yamazaki Masashi
Published: August 2022

We performed salvage surgery on a patient with kyphotic deformity after anterior cervical fusion with a tortuous vertebral artery (VA). A 69-year-old woman had undergone anterior cervical corpectomy and fusion 12 years ago. Her cervical alignment gradually became kyphotic because of bone graft collapse. Ten years after surgery, she experienced severe neck pain, recurrence of myelopathic symptoms and difficulty in keeping her head straight. The patient was diagnosed with rigid cervical kyphosis at C4–6 vertebral levels, with the right tortuous VA invaginating into the C4 vertebral body. We selected a three-stage, anterior–posterior–anterior approach to reduce cervical alignment. The key to a successful surgery in this case was to retract the tortuous VA within the C4 vertebral body, followed by total uncinectomy. Careful preoperative VA evaluation was a decisive factor in surgical planning.
Recurrent urethral stricture with dual lumen managed by a single stage dorsal Onlay buccal mucosal graft Urethroplasty: a case report
Authors: Alkhayal Abdullah , Alrabeeah Khalid , Alsaikhan Bader H , Alathel Abdulaziz , Barayan Fahad R , Alsaghyir Abdullah
Published: August 2022

Urethral stricture is defined as any abnormal narrowing throughout the entire length of the male urethra. Anterior urethral stricture is the most common site which accounts for more than 90% of cases in developed countries. One of the possible long-term outcomes of urethral stricture treatment is stricture recurrence. Refractory urethral strictures to initial management present surgical challenges to the reconstructive surgeon. It has been reported in the literature that buccal mucosal grafts in complex anterior urethral strictures have lately become a well-established management modality for bulbar and penile urethral strictures. Here, we are presenting an interesting case of a patient with a dual lumen urethra due to recurrent urethral stricture.
Management of sarcopenia in patients with rheumatoid arthritis
Authors: Torii Mie , Itaya Takahiro , Minamino Hiroto , Katsushima Masao , Fujita Yoshihito , Tanaka Hiroki , Oshima Yohei , Watanabe Ryu , Ito Hiromu , Arai Hidenori , Hashimoto Motomu
Published: August 2022

This review summarizes the evidence for the management of sarcopenia in patients with rheumatoid arthritis (RA) in terms of drugs, exercise, and nutrition. Sarcopenia is a decrease in skeletal muscle mass and muscle strength or physical function. The prevalence of sarcopenia in patients with RA is higher than that in the general population. The treatment and management of sarcopenia in patients with RA are clinically important for long-term prognosis. One of the mechanisms of muscle metabolism is the pro-inflammatory cytokine pathway, which involves tumour necrosis factor α and interleukin-6, and is a common pathway in the pathogenesis of RA. Thus, tumour necrosis factor α and interleukin-6 inhibitors may play a potential role in controlling sarcopenia. In exercise therapy, a combination of moderate resistance and aerobic exercise may be effective in improving muscle strength, muscle mass, and physical function; however, intense exercise may exacerbate the inflammatory response in RA. Regarding nutrition, protein intake is generally considered beneficial, but other nutrients such as vitamin D and carotenoids have also been studied. Overall, there remains a lack of concrete evidence on sarcopenia treatment and management in patients with RA from any perspective; more longitudinal and intervention studies are needed in the future.
Label-free hyperspectral imaging and deep-learning prediction of retinal amyloid β-protein and phosphorylated tau
Authors: Du Xiaoxi , Koronyo Yosef , Mirzaei Nazanin , Yang Chengshuai , Fuchs Dieu-Trang , Black Keith L , Koronyo-Hamaoui Maya , Gao Liang
Published: August 2022

Alzheimer’s disease (AD) is a major risk for the aging population. The pathological hallmarks of AD—an abnormal deposition of amyloid β-protein (Aβ) and phosphorylated tau (pTau)—have been demonstrated in the retinas of AD patients, including in prodromal patients with mild cognitive impairment (MCI). Aβ pathology, especially the accumulation of the amyloidogenic 42-residue long alloform (Aβ42), is considered an early and specific sign of AD, and together with tauopathy, confirms AD diagnosis. To visualize retinal Aβ and pTau, state-of-the-art methods use fluorescence. However, administering contrast agents complicates the imaging procedure. To address this problem from fundamentals, ex-vivo studies were performed to develop a label-free hyperspectral imaging method to detect the spectral signatures of Aβ42 and pS396-Tau, and predicted their abundance in retinal cross-sections. For the first time, we reported the spectral signature of pTau and demonstrated an accurate prediction of Aβ and pTau distribution powered by deep learning. We expect our finding will lay the groundwork for label-free detection of AD.
Emergency Contraception: Access and Challenges at Times of Uncertainty
Authors: Stein Richard A. , Deverakonda Abhi N. , Katz Adi , Schmidt Elizabeth O.
Published: August 2022

Background:

The UN Commission on Life-Saving Commodities for Women and Children identified emergency contraceptive pills as 1 of the 13 essential underused, low-cost, and high-impact commodities that could save the lives of millions of women and children worldwide. In the US, 2 emergency contraceptive regimens are currently approved, and their most plausible mechanism of action involves delaying and/or inhibiting ovulation.

Areas of uncertainty:

Abortion and contraception are recognized as essential components of reproductive health care. In the US, in the wake of theDobbs v. Jackson Women's Health OrganizationSupreme Court decision on June 24, 2022, 26 states began to or are expected to severely restrict abortion. It is anticipated that these restrictions will increase the demand for emergency contraception (EC). Several obstacles to EC access have been described, and these include cost, hurdles to over-the-counter purchase, low awareness, myths about their mechanisms of action, widespread misinformation, and barriers that special populations face in accessing them. The politicization of EC is a major factor limiting access. Improving sex education and health literacy, along with eHealth literacy, are important initiatives to improve EC uptake and access.

Data Sources:

PubMed, The Guttmacher Institute, Society of Family Planning, American College of Obstetricians and Gynecologists, the World Health Organization, The United Nations.

Therapeutic Advances:

A randomized noninferiority trial showed that the 52 mg levonorgestrel intrauterine device was noninferior to the copper intrauterine device when used as an EC method in the first 5 days after unprotected intercourse. This is a promising and highly effective emergency contraceptive option, particularly for overweight and obese patients, and a contraceptive option with a different bleeding profile than the copper intrauterine device.

Conclusions:

EC represents an important facet of medicine and public health. The 2 medical regimens currently approved in the US are very effective, have virtually no medical contraindications, and novel formulations are actively being investigated to make them more convenient and effective for all patient populations. Barriers to accessing EC, including the widespread presence ofcontraception deserts, threaten to broaden and accentuate the already existing inequities and disparities in society, at a time when they have reached the dimensions of a public health crisis.
Precision medicine for developmental and epileptic encephalopathies in Africa – strategies for a resource-limited setting
Authors: Esterhuizen Alina I. , Tiffin Nicki , Riordan Gillian , Wessels Marie , Burman Richard J. , Aziz Miriam C. , Calhoun Jeffrey D. , Gunti Jonathan , Amiri Ezra E. , Ramamurthy Aishwarya , Bamshad Michael J. , Nickerson Deborah A. , Mefford Heather C. , Ramesar Raj , Wilmshurst Jo M. , Carvill Gemma L.
Published: August 2022

Purpose

Sub-Saharan Africa bears the highest burden of epilepsy worldwide. A presumed proportion is genetic, but this aetiology is buried under the burden of infections and perinatal insults, in a setting of limited awareness and few options for testing. Children with developmental and epileptic encephalopathies (DEEs), are most severely affected by this diagnostic gap in Africa, as the rate of actionable findings is highest in DEE-associated genes.

Methods

We tested 235 genetically naïve South African children diagnosed with/possible DEE, using gene panels, exome sequencing and chromosomal microarray. Statistical comparison of electroclinical features in children with and without candidate variants was performed to identify characteristics most likely predictive of a positive genetic finding.

Results

Of 41/235 children with likely/pathogenic variants, 26/235 had variants supporting precision therapy. Multivariate regression modelling highlighted neonatal or infantile-onset seizures and movement abnormalities as predictive of a positive genetic finding. We used this, coupled with an emphasis on precision medicine outcomes, to propose the pragmatic “Think-Genetics” strategy for early recognition of a possible genetic aetiology.

Conclusion

Our findings emphasise the importance of an early genetic diagnosis in DEE. We designed the “Think-Genetics” strategy for early recognition, appropriate interim management and genetic testing for DEE in resource-constrained settings.
RNA-triggered protein cleavage and cell death by the RNA-guided type III-E CRISPR-Cas nuclease-protease complex
Authors: Kato Kazuki , Okazaki Sae , Schmitt-Ulms Cian , Jiang Kaiyi , Zhou Wenyuan , Ishikawa Junichiro , Isayama Yukari , Adachi Shungo , Nishizawa Tomohiro , Makarova Kira S. , Koonin Eugene V. , Abudayyeh Omar O. , Gootenberg Jonathan S. , Nishimasu Hiroshi
Published: August 2022

The type III-E Cas7-11 effector nuclease forms a complex with a CRISPR RNA (crRNA) and the putative caspase-like protease Csx29, catalyzes crRNA-guided target RNA cleavage, and has been used for RNA targeting in eukaryotic cells. Here, we report cryo-electron microscopy structures of the Cas7-11–crRNA–Csx29 complex with and without target RNA, and demonstrate that target RNA binding induces a conformational change in Csx29 and results in the protease activation. Biochemical analysis confirmed that Cas7-11-bound Csx29 cleaves Csx30 in a target RNA-dependent manner. Reconstitution of the system in bacteria uncovered Csx30-dependent cellular toxicity regulated by Csx31, and that Csx29-mediated cleavage produces toxic Csx30 fragments, promoting cell death. We find that Csx30 can bind both Csx31 and the associated sigma factor RpoE, suggesting Csx30 can inhibit RpoE and modulate cellular stress response towards infection. Overall, the RNA-guided nuclease-protease activities of the Cas7-11–Csx29 effector complex facilitate protease-based programmed cell death.
The effector recognition by synthetic sensor NLR receptors requires the concerted action of multiple interfaces within and outside the integrated domain
Authors: Zhang Xin , Liu Yang , Yuan Guixin , Wang Dongli , Zhu Tongtong , Wu Xuefeng , Ma Mengqi , Guo Liwei , Guo Hailong , Bhadauria Vijai , Liu Junfeng , Peng You-Liang
Published: August 2022

Plant sensor nucleotide-binding leucine-rich repeat (NLR) receptors detect pathogen effectors through their integrated domains (IDs). The RGA5 sensor NLR recognizes its corresponding effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae through direct binding to its heavy metal-associated (HMA) ID to trigger the RGA4 helper NLR-dependent resistance in rice. Here we report a mutant of RGA5 named RGA5HMA5 that confers complete resistance in transgenic rice plants to the M. oryzae strains expressing the noncorresponding effector AVR-PikD. RGA5HMA5 carries three engineered interfaces, two of which lie in the HMA ID and the other in the C-terminal Lys-rich stretch tailing the ID. However, the RGA5 variants having one or two of the three interfaces, including replacing all the Lys residues with Glu residues in the Lys-rich stretch, failed to activate RGA4-dependent cell death of rice protoplasts. Altogether, this work demonstrates that sensor NLRs require a concerted action of multiple surfaces within and outside the IDs to both recognize noncorresponding effectors and activate helper NLR-mediated resistance, and has implications in structure-guided designing of sensor NLRs.
Deep-Worm-Tracker: Deep Learning Methods for Accurate Detection and Tracking for Behavioral Studies in C. elegans
Authors: Banerjee Shoubhik Chandan , Khan Khursheed Ahmad , Sharma Rati
Published: August 2022

Accurate detection and tracking of model organisms such as C. elegans worms remains a fundamental task in behavioral studies. Traditional Machine Learning (ML) and Computer Vision (CV) methods produce poor detection results and suffer from repeated ID switches during tracking under occlusions and noisy backgrounds. Using Deep Learning (DL) methods, the task of animal tracking from video recordings, like those in camera trap experiments, has become much more viable. The large amount of data generated in ethological studies, makes such models suitable for real world scenarios in the wild. We propose Deep-Worm-Tracker, an end to end DL model, which is a combination of You Only Look Once (YOLOv5) object detection model and Strong Simple Online Real Time Tracking (Strong SORT) tracking backbone that is highly accurate and provides tracking results in real time inference speeds. Present literature has few solutions to track animals under occlusions and even fewer publicly available large scale animal re-ID datasets. Thus, we also provide a worm re-ID dataset to minimize worm ID switches, which, to the best of our knowledge, is first-of-its-kind for C. elegans. We are able to track worms at a mean Average Precision (mAP@0.5) > 98% within just 9 minutes of training time with inference speeds of 9-15 ms for worm detection and on average 27 ms for worm tracking. Our tracking results show that Deep-Worm-Tracker is well suited for ethological studies involving C. elegans.
Modeling concentration-dependent phase separation processes involving peptides and RNA via residue-based coarse-graining
Authors: Valdes-Garcia Gilberto , Heo Lim , Lapidus Lisa J. , Feig Michael
Published: August 2022

Biomolecular condensation, especially liquid-liquid phase separation, is an important physical process with relevance for a number of different aspects of biological functions. Key questions of what drives such condensation, especially in terms of molecular composition, can be addressed via computer simulations, but the development of computationally efficient, yet physically realistic models has been challenging. Here, the coarse-grained model COCOMO is introduced that balances the polymer behavior of peptides and RNA chains with their propensity to phase separate as a function of composition and concentration. COCOMO is a residue-based model that combines bonded terms with short- and long-range terms, including a Debye-Hückel solvation term. The model is highly predictive of experimental data on phase-separating model systems. It is also computationally efficient and can reach the spatial and temporal scales on which biomolecular condensation is observed with moderate computational resources.
Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import
Authors: Nashed S , El Barbry H , Benchouaia M , Dijoux-Maréchal A , Ruiz Gutierrez N , Gaulier L , Chevreux G , Le Crom S , Palancade B , Devaux F , Laine E , Garcia M
Published: August 2022

N-terminal ends of polypeptides are critical for the selective co-translational recruitment of N-terminal modification enzymes. However, it is unknown whether specific N-terminal signatures differentially regulate protein fate according to their cellular functions. In this work, we developed an in-silico approach to detect functional preferences in cellular N-terminomes, and identified inS. cerevisiaemore than 200 Gene Ontology terms with specific N-terminal signatures. In particular, we discovered that Mitochondrial Targeting Sequences (MTS) show a strong and specific over-representation at position 2 of hydrophobic residues known to define potential substrates of the N-terminal acetyltransferase NatC. We validated mitochondrial precursors as co-translational targets of NatC by selective purification of translating ribosomes, and found that their N-terminal signature is conserved in Saccharomycotina yeasts. Finally, systematic mutagenesis of the position 2 in a prototypal yeast mitochondrial protein confirmed its critical role in mitochondrial protein import. Our work highlights the hydrophobicity of MTS N-terminal residues and their modification by NatC as critical features for the definition of the mitochondrial proteome, providing a molecular explanation for mitochondrial defects observed in yeast or human NatC-depleted cells. Functional mapping of N-terminal residues thus has the potential to support the discovery of novel mechanisms of protein regulation or targeting.
Ecology drives the observed spectrum of hydrophobin protein diversity across Kingdom Fungi
Authors: Lovett Brian , Kasson Matt T. , Gandier Julie-Anne
Published: August 2022

1.

Hydrophobins mediate the interactions between fungi and the elements of their ecosystem via assembly at interfaces serving a wide range of diverse functions. As such, these proteins can be seen as a means by which fungi not only adapt to a pre-existing environment, but also actively participate in the construction of their own ecological niches. Through this lens, we provide an expansive hydrophobin survey across the ecological breadth of Kingdom Fungi and advance the view that hydrophobins are best defined as a generic molecular structure with shared core structural features that accommodate a remarkable diversity of amino acid sequences. We examine the relationship between hydrophobin sequences, fungus phylogeny, and associated ecology from 45 fungal proteomes predicted from genomes spanning eight phyla and more than 25 orders. To capture the full spectrum of the hydrophobin amino acid sequence space mapped by our study, we describe the family as a continuum of overlapping hidden Markov models (HMMs), each HMM representing clusters of sequence similarity spanning existing hydrophobin classes. Overall, our approach uncovered ecology as a major driver of hydrophobin diversification, further expanded the known hydrophobins beyond Dikarya, and uncovered evidence extending the possibilities for their function from exclusively extracellular to include intracellular. In addition, we identified novel core groups of cysteine-rich proteins whose conservation across fungi suggest they play key ecological roles. Together, our work offers an ontological framework that captures the diversity of hydrophobin amino acid sequences and highlights the need to revisit challenging fundamental questions regarding hydrophobins to achieve a mechanistic understanding of their function as emerging from assembly within an ecosystem.
Remarkable sex-specific differences at Single-Cell Resolution in Neonatal Hyperoxic Lung Injury
Authors: Cantu A , Cantu M , Dong X , Leek C , Sajti E , Lingappan K
Published: August 2022

Exposure to supraphysiological concentrations of oxygen (hyperoxia) predisposes to bronchopulmonary dysplasia (BPD), which is characterized by abnormal alveolarization and pulmonary vascular development, in preterm neonates. Neonatal hyperoxia exposure is used to recapitulate the phenotype of human BPD in murine models. Male sex is considered an independent predictor for the development of BPD, but the main mechanisms underlying sexually dimorphic outcomes are unknown. Our objective was to investigate sex-specific and cell-type specific transcriptional changes that drive injury in the neonatal lung exposed to hyperoxia at single-cell resolution and delineate the changes in cell-cell communication networks in the developing lung. We used single cell RNA sequencing (scRNAseq) to generate transcriptional profiles of >35000 cells isolated from the lungs of neonatal male and female C57BL/6 mice exposed to 95% FiO2 between PND1-5 (saccular stage of lung development) or normoxia and euthanized at PND7 (alveolar stage of lung development). ScRNAseq identified 22 cell clusters with distinct populations of endothelial, epithelial, mesenchymal, and immune cells. Our data identified that the distal lung vascular endothelium (composed of aerocytes and general capillary endothelial cells) is exquisitely sensitive to hyperoxia exposure with the emergence of an intermediate capillary endothelial population with both aCaP and gCaP markers. We also identified a myeloid derived suppressor cell population from the lung neutrophils. Sexual dimorphism was evident in all lung cell subpopulations but was striking among the lung immune cells. Finally, we identified that the specific intercellular communication networks and the ligand-receptor pairs that are impacted by neonatal hyperoxia exposure.
SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model
Authors: Serafini Randal A. , Frere Justin J. , Zimering Jeffrey , Giosan Ilinca M. , Pryce Kerri D. , Golynker Ilona , Panis Maryline , Ruiz Anne , tenOever Benjamin , Zachariou Venetia
Published: August 2022

Despite being largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and long-lasting phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster infection model to characterize the effects of SARS-CoV-2 versus Influenza A virus (IAV) infection on the sensory nervous system. Efforts to detect the presence of virus in the cervical/thoracic spinal cord and dorsal root ganglia (DRGs) demonstrated detectable levels of SARS-CoV-2 by quantitative PCR and RNAscope uniquely within the first 24 hours of infection. SARS-CoV-2-infected hamsters demonstrated mechanical hypersensitivity during acute infection; intriguingly, this hypersensitivity was milder, but prolonged when compared to IAV-infected hamsters. RNA sequencing (RNA-seq) of thoracic DRGs from acute infection revealed predominantly neuron-biased signaling perturbations in SARS-CoV-2-infected animals as opposed to type I interferon signaling in tissue derived from IAV-infected animals. RNA-seq of 31dpi thoracic DRGs from SARS-CoV-2-infected animals highlighted a uniquely neuropathic transcriptomic landscape, which was consistent with substantial SARS-CoV-2-specific mechanical hypersensitivity at 28dpi. Ontology analysis of 1, 4, and 30dpi RNA-seq revealed novel targets for pain management, such as ILF3. Meta-analysis of all SARS-CoV-2 RNA-seq timepoints against preclinical pain model datasets highlighted both conserved and unique pro-nociceptive gene expression changes following infection. Overall, this work elucidates novel transcriptomic signatures triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities while also highlighting several therapeutic targets for alleviation of infection-induced hypersensitivity.

One Sentence Summary

SARS-CoV-2 infection results in an interferon-associated transcriptional response in sensory tissues underlying time-dependent hypersensitivity.
RNA Immunoprecipitation and Sequencing of Isolated RNAs (RIP-SIR) Identifies Endogenous miRNA-Target Interactions
Authors: Wells Julie , Srivastava Anuj , Maser Richard S. , Kesharwani Rupesh , Sarsani Vishal Kumar , Daigle Sandra L. , Lynch Ryan P. , Munger Heidi J. , Doty Rosalinda , Saxl Ruth L. , Bult Carol J.
Published: August 2022

MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression in species ranging from plants to mammals. Unraveling the complex networks of miRNA-mediated regulation of gene expression requires the ability to identify the mRNA targets of individual miRNAs in native cellular contexts. Here we describe RIP-SIR, an unbiased genome-wide method for identifying interactions between endogenous miRNAs and their targets in almost any tissue or cell type.
Detection of Frog virus 3 via the system integrating RPA-CRISPR/Cas12a-SPM with deep learning
Authors: Lei Zhengyang , Lian Lijin , Zhang Likun , Wei Jiazhang , Liu Changyue , Liu Hong , Liu Ying , Du Zhicheng , Yuan Xi , Zhong Xiaoyun , Gul Ijaz , Zhang Haihui , Wang Chuhui , Zhai Shiyao , Pandey Vijay , Zhang Canyang , Xing Xinhui , Deng Lin , Yu Dongmei , He Qian , Qin Peiwu
Published: August 2022

Frog virus 3 (FV3, generaRanavirus, familyIridoviridae), a double-stranded DNA virus, results in irreparable damage to biodiversity and significant economic losses to aquaculture. Although the existing FV3 detection methods are of high sensitivity and specificity, the complex procedure and requirement of expensive instruments limit their practical implantation. Herein, we develop a fast, easy-to-implement, highly sensitive, and point-of-care (POC) detection system for FV3. Combining recombinase polymerase amplification (RPA) and CRISPR/Cas12a, we achieve a limit of detection (LoD) of 100 aM (60.2 copies/μL) by optimizing RPA primers and CRISPR RNAs (crRNAs). For POC detection, we build a smartphone microscopy (SPM) and achieve an LoD of 10 aM within 40 minutes. Four positive animal-derived samples with a quantitation cycle (Cq) value of quantitative PCR (qPCR) in the range of 13 to 32 are detectable by the proposed system. In addition, we deploy deep learning models for binary classification (positive or negative samples) and multiclass classification (different concentrations of FV3 and negative samples), achieving 100% and 98.75% accuracy, respectively. Without temperature regulation and expensive equipment, RPA-CRISPR/Cas12a combined with a smartphone readout and artificial intelligence (AI) assisted classification shows great potential for FV3 detection. This integrated system holds great promise for POC detection of aquatic DNA pathogens.

Highlights

An integrated DNA detection system is developed by combining RPA, CRISPR/Cas12a, smartphone microscopy, and deep learning.

The LoD of frog virus 3 is 10 aM within 40 min.

The detection system shows good performance on animal-derived samples.