Measurement of the α-Particle Monopole Transition Form Factor Challenges Theory: A Low-Energy Puzzle for Nuclear Forces?

We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron scattering experiment in a broad Q^{2} range (from 0.5 to 5.0 fm^{-2}). The precision of the new data dramatically supersedes that of older sets of data, each covering only a portion of the Q^{2} range. The new data allow the determination of two coefficients in a low-momentum expansion, leading to a new puzzle. By confronting experiment to state-of-the-art theoretical calculations, we observe that modern nuclear forces, including those derived within chiral effective field theory that are well tested on a variety of observables, fail to reproduce the excitation of the α particle.

Gonadoblastoma Y locus genes expressed in germ cells of individuals with dysgenetic gonads and a Y chromosome in their karyotypes include DDX3Y and TSPY.

STUDY QUESTION: Which Y genes mapped to the 'Gonadoblastoma Y (GBY)' locus on human Y chromosome are expressed in germ cells of individuals with some Differences of Sexual Development (DSD) and a Y chromosome in their karyotype (DSD-XY groups)? SUMMARY ANSWER: The GBY candidate genes DDX3Y and TSPY are expressed in the germ cells of DSD-XY patients from distinct etiologies: patients with mixed gonadal dysgenesis (MGD) and sex chromosome mosaics (45,X0/46,XY; 46,XX/46,XY); patients with complete androgen insensitivity (CAIS), patients with complete gonadal dysgenesis (CGD; e.g. Swyer syndrome). WHAT IS KNOWN ALREADY: A GBY locus was proposed to be present on the human Y chromosome because only DSD patients with a Y chromosome in their karyotype have a high-although variable-risk (up to 55%) for germ cell tumour development. GBY was mapped to the proximal part of the short and long Y arm. TSPY located in the proximal part of the short Y arm (Yp11.1) was found to be a strong GBY candidate gene. It is expressed in the germ cells of DSD-XY patients with distinct etiologies but also in foetal and pre-meiotic male spermatogonia. However, the GBY region extends to proximal Yq11 and therefore includes probably more than one candidate gene. STUDY DESIGN, SIZE, DURATION: Protein expression of the putative GBY candidate gene in proximal Yq11, DDX3Y, is compared with that of TSPY in serial gonadal tissue sections of 40 DSD-XY individuals from the three DSD patient groups (MGD, Complete Androgen Insensitivity Syndrome [CAIS], CGD) with and without displaying malignancy. Expression of OCT3/4 in the same tissue samples marks the rate of pluripotent germ cells. PARTICIPANTS/MATERIALS, SETTING, METHOD: A total of 145 DSD individuals were analysed for the Y chromosome to select the DSD-XY subgroup. PCR multiplex assays with Y gene specific marker set score for putative microdeletions in GBY Locus. Immunohistochemical experiments with specific antisera mark expression of the GBY candidate proteins, DDX3Y, TSPY, in serial sections of the gonadal tissue samples; OCT3/4 expression analyses in parallel reveal the pluripotent germ cell fraction. MAIN RESULTS AND THE ROLE OF CHANCE: Similar DDX3Y and TSPY protein expression patterns were found in the germ cells of DSD-XY patients from each subgroup, independent of age. In CAIS patients OCT3/4 expression was often found only in a fraction of these germ cells. This suggest that GBY candidate proteins are also expressed in the non-malignant germ cells of DSD-XY individuals like in male spermatogonia. LIMITATIONS, REASONS FOR CAUTION: Variation of the expression profiles of GBY candidate genes in the germ cells of some DSD-XY individuals suggests distinct transcriptional and translational control mechanisms which are functioning during expression of these Y genes in the DSD-XY germ cells. Their proposed GBY tumour susceptibility function to transform these germ cells to pre-malignant GB/Germ Cell Neoplasia in Situ (GB/GCNIS) cells seems therefore to be limited and depending on their state of pluripotency. WIDER IMPLICATIONS OF THE FINDINGS: These experimental findings are of general importance for each individual identified in the clinic with DSD and a Y chromosome in the karyotype. To judge their risk of germ cell tumour development, OCT3/4 expression analyses on their gonadal tissue section is mandatory to reveal the fraction of germ cells still being pluripotent. Comparative expression analysis of the GBY candidate genes can be helpful to reveal the fraction of germ cells with genetically still activated Y chromosomes contributing to further development of malignancy if at high expression level. STUDY FUNDING/COMPETING INTEREST(S): This research project was supported by a grant (01GM0627) from the BMBF (Bundesministerium für Bildung und Forschung), Germany to P.H.V. and B.B. The authors have no competing interests.

First Measurement of the Q

We report on the first Q^{2}-dependent measurement of the beam-normal single spin asymmetry A_{n} in the elastic scattering of 570 MeV vertically polarized electrons off ^{12}C. We cover the Q^{2} range between 0.02 and 0.05 GeV^{2}/c^{2} and determine A_{n} at four different Q^{2} values. The experimental results are compared to a theoretical calculation that relates A_{n} to the imaginary part of the two-photon exchange amplitude. The result emphasizes that the Q^{2} behavior of A_{n} given by the ratio of the Compton to charge form factors cannot be treated independently of the target nucleus.

Prognostic value of MACC1 and proficient mismatch repair status for recurrence risk prediction in stage II colon cancer patients: the BIOGRID studies.

BACKGROUND: We assessed the novel MACC1 gene to further stratify stage II colon cancer patients with proficient mismatch repair (pMMR). PATIENTS AND METHODS: Four cohorts with 596 patients were analyzed: Charité 1 discovery cohort was assayed for MACC1 mRNA expression and MMR in cryo-preserved tumors. Charité 2 comparison cohort was used to translate MACC1 qRT-PCR analyses to FFPE samples. In the BIOGRID 1 training cohort MACC1 mRNA levels were related to MACC1 protein levels from immunohistochemistry in FFPE sections; also analyzed for MMR. Chemotherapy-naïve pMMR patients were stratified by MACC1 mRNA and protein expression to establish risk groups based on recurrence-free survival (RFS). Risk stratification from BIOGRID 1 was confirmed in the BIOGRID 2 validation cohort. Pooled BIOGRID datasets produced a best effect-size estimate. RESULTS: In BIOGRID 1, using qRT-PCR and immunohistochemistry for MACC1 detection, pMMR/MACC1-low patients had a lower recurrence probability versus pMMR/MACC1-high patients (5-year RFS of 92% and 67% versus 100% and 68%, respectively). In BIOGRID 2, longer RFS was confirmed for pMMR/MACC1-low versus pMMR/MACC1-high patients (5-year RFS of 100% versus 90%, respectively). In the pooled dataset, 6.5% of patients were pMMR/MACC1-low with no disease recurrence, resulting in a 17% higher 5-year RFS [95% confidence interval (CI) (12.6%-21.3%)] versus pMMR/MACC1-high patients (P = 0.037). Outcomes were similar for pMMR/MACC1-low and deficient MMR (dMMR) patients (5-year RFS of 100% and 96%, respectively). CONCLUSIONS: MACC1 expression stratifies colon cancer patients with unfavorable pMMR status. Stage II colon cancer patients with pMMR/MACC1-low tumors have a similar favorable prognosis to those with dMMR with potential implications for the role of adjuvant therapy.

Natural conception rates in subfertile couples following fertility awareness training.

PURPOSE: To analyze cumulative pregnancy rates of subfertile couples after fertility awareness training. METHODS: A prospective observational cohort study followed 187 subfertile women, who had received training in self-observation of the fertile phase of the menstrual cycle with the Sensiplan method, for 8 months. The women, aged 21-47 years, had attempted to become pregnant for 3.5 years on average (range 1-8 years) before study entry. Amenorrhea, known tubal occlusion and severe male factor had been excluded. An additional seven women, who had initially been recruited, became pregnant during the cycle immediately prior to Sensiplan training: this is taken to be the spontaneous pregnancy rate per cycle in the cohort in the absence of fertility awareness training. RESULTS: The cumulative pregnancy rate of subfertile couples after fertility awareness training was 38% (95% CI 27-49%; 58 pregnancies) after eight observation months, which is significantly higher than the estimated basic pregnancy rate of 21.6% in untrained couples in the same cohort. For couples who had been seeking to become pregnant for 1-2 years, the pregnancy rate increased to 56% after 8 months. A female age above 35 (cumulative pregnancy rate 25%, p = 0.06), couples who had attempted to become pregnant for more than 2 years (cumulative pregnancy rate 17%, p < 0.01), all significantly reduce the chances of conceiving naturally at some point. CONCLUSIONS: Training women to identify their fertile window in the menstrual cycle seems to be a reasonable first-line therapy in the management of subfertility.

[Postoperative implant-associated osteomyelitis of the shoulder: Hardware-retaining revision concept using temporary drainage]. / Postoperative implantatassoziierte Osteitis am Schultergürtel: Materialerhaltendes Revisionskonzept mit Einlage einer Dauerdrainage.

BACKGROUND: Posttraumatic and postoperative osteomyelitis (PPO) is a subgroup of bone infections with increasing importance. However, to date no standardized reoperation concept exists particularly for patients with PPO of the shoulder region. Therefore the purpose of this study was to evaluate a revision concept including débridement, irrigation, and insertion of temporary drainage with hardware retention until healing. PATIENTS AND METHODS: A total of 31 patients with PPO were included with a proximal humerus fracture (n = 14), clavicle fracture (n = 10), or AC-joint separation (n = 7). In all, 27 of these patients could be followed for > 1 year. RESULTS: Hardware retention until fracture or ligament healing could be achieved in > 83%. Six patients required follow-up débridement due to recurrent infections, but then were unremarkable. Clinical outcome showed excellent Constant scores (91.6 ± 2.8). CONCLUSION: A cost-efficient, simple, and successful revision concept for patients with PPO of the shoulder region is described.

Hypoglycaemia and predisposing factors among clinical subgroups treated with intensive insulin therapy.

BACKGROUND: In previous studies, conflicting intensive insulin therapy (IIT) results have been observed, whereby IIT-related mortality seems to be lower in specific clinical subgroups. The aim of this study was to assess differences in glycaemic control, the risk of critical hypoglycaemia (≤ 2.2 mmol/l), the associated predisposing factors, and the in-hospital mortality in different clinical subgroups treated with IIT. METHODS: Prospective, observational study in a university-affiliated intensive care unit (ICU) conducted from 2004 to 2005. All patients (n = 1667) belonging to one of the six most common surgical intervention groups (cardiac, neuro, abdominal, vascular, orthopaedic, and spinal surgeries) and medical patients were included. IIT was performed with a target blood glucose level of 4.4-7.8 mmol/l. Different indices were analysed to evaluate glucose control and glycaemic variability. RESULTS: The rate of critical hypoglycaemia was significantly different within the different clinical subgroups and varied from 0.8% to 4.5%. Similar results were obtained for hyperglycaemia. Multivariable analyses for the predisposing factors of critical hypoglycaemia showed a heterogeneous distribution pattern among the different clinical subgroups. Similar results were obtained for the risk factors of in-hospital mortality. CONCLUSION: The risk of critical hypoglycaemia and the associated predisposing factors depended on the clinical subgroup involved. Critical hypoglycaemia is a potential threat for our patients, and the high risk of critical hypoglycaemia in some clinical subgroups appeared to reverse the benefits of IIT. As a result, it is crucial that the different subgroups involved in a study are defined to further interpret the potential benefits of IIT and the risk of critical hypoglycaemia.

Microcantilever sensors coated with a sensitive polyaniline layer for detecting volatile organic compounds.

This paper describes a silicon cantilever sensor coated with a conducting polymer layer. The mechanical response (deflection) of the bimaterial (the coated microcantilever) was investigated under the influence of several volatile compounds-methanol, ethanol, acetone, propanol, dichloroethane, toluene and benzene. The variations in the deflection of the coated and uncoated microcantilevers when exposed to volatile organic compounds were evaluated, and the results indicated that the highest sensitivity was obtained with the coated microcantilever and methanol. The uncoated microcantilever was not sensitive to the volatile organic compounds. An increase in the concentration of the volatile organic compound resulted in higher deflections of the microcantilever sensor. The sensor responses were reversible, sensible, rapid and proportional to the volatile concentration.

Low androgen signaling rescues genome integrity with innate immune response by reducing fertility in humans.

Development of the gonads under complex androgen regulation is critical for germ cells specification. In this work we addressed the relationship between androgens and genomic integrity determining human fertility. We used different study groups: individuals with Differences of Sex Development (DSD), including Complete Androgen Insensitivity Syndrome (CAIS) due to mutated androgen receptor (AR), and men with idiopathic nonobstructive azoospermia. Both showed genome integrity status influenced by androgen signaling via innate immune response activation in blood and gonads. Whole proteome analysis connected low AR to interleukin-specific gene expression, while compromised genome stability and tumorigenesis were also supported by interferons. AR expression was associated with predominant DNA damage phenotype, that eliminated AR-positive Sertoli cells as the degeneration of gonads increased. Low AR contributed to resistance from the inhibition of DNA repair in primary leukocytes. Downregulation of androgen promoted apoptosis and specific innate immune response with higher susceptibility in cells carrying genomic instability.

Hericium ophelieae sp. nov., a novel species of Hericium (Basidiomycota: Russulales, Hericiaceae) from the Southern Afrotemperate forests of South Africa.

A novel species of Hericium was recently collected in the Afrotemperate forests (Knysna - Amatole region) of Southern Africa. The novel species shares many similar, dentate features common to other species in Hericium, and its basidiome first appears stark white and yellows with age. However, the substrate choice and gloeocystidia and basidiospore sizes of the specimens collected were distinct from other Hericium species. This was confirmed by sequencing the ITS and 28S genetic markers, respectively. The novel species is described as Hericium ophelieae sp. nov. and appears unique as it grows on hardwoods indigenous to Southern Africa. The species has larger basidiospores and wider gloeocystidia compared to its closest relative. H. ophelieae sp. nov. is the first endemic species of the medicinal mushroom genus Hericium to be described from Southern Africa, and the second to be described from Africa, after its closest relative, H. bembedjaense, which was isolated in Cameroon. Although this is the first Hericium to be described from the Southern African region, there are likely others to be discovered, and this study highlights the need for further research into the fungal diversity of Afrotemperate environments.

Development of a Business Model Resilience Framework for Managers and Strategic Decision-makers.

Following the massive impact of the Covid-19 pandemic on the global economy and on small and medium-sized enterprises (SMEs) in particular, the concept of resilience has experienced a renaissance. As an organizational concept, business model resilience describes the extent to which an organization can maintain or quickly recover its value proposition despite unexpected current or future disruptions (Palzkill-Vorbeck 2018). Although research has been conducted in this area for decades, there is still a lack of a unified framework that brings together the findings from research and links them to organizational practice. The paper addresses this gap by developing a framework for business model resilience and demonstrating its practical relevance for organizational performance during the Covid-19 pandemic in 2020. The framework includes 11 factors that characterize the resilience of an organization's business model. For managers and decision-makers, the framework is an opportunity to assess and improve the resilience of their organizations. For researchers, the framework is an important foundation for transferring the concept of business model resilience into organizational practice.

A functional model related to cytochrome c oxidase and its electrocatalytic four-electron reduction of O2.

A cytochrome c oxidase model that consists of a cobalt(II) porphyrin with a copper(I) triazacyclononane macrocycle fastened on the distal face and an imidazole covalently attached to the proximal face has been synthesized and characterized. Redox titrations with molecular oxygen (O2) and cobaltocene were carried out, and O2 was found to bind irreversibly in a 1:1 ratio to the model compound. This O2 adduct (a bridged peroxide) can be fully reduced to the deoxygenated form with four equivalents of cobaltocene. The model compound was adsorbed on an edge-plane graphite electrode, and rotating ring-disk voltammetry was used to monitor the electrocatalytic reduction of O2. Four-electron reduction of O2 was observed at physiological pH.

In vivo implantation of a tissue engineered stem cell seeded hemi-laryngeal replacement maintains airway, phonation, and swallowing in pigs.

Laryngeal functional impairment relating to swallowing, vocalisation, and respiration can be life changing and devastating for patients. A tissue engineering approach to regenerating vocal folds would represent a significant advantage over current clinical practice. Porcine hemi-larynx were de-cellularised under negative pressure. The resultant acellular scaffold was seeded with human bone marrow derived mesenchymal stem cells and primary human epithelial cells. Seeded scaffolds were implanted orthotopically into a defect created in the thyroid cartilage in 8 pigs and monitored in vivo for 2 months. In vivo assessments consisted of mucosal brushing and bronchoscopy at 1, 2, 4, and 8 weeks post implantation followed by histological evaluation post termination. The implanted graft had no adverse effect on respiratory function in 6 of the 8 pigs; none of the pigs had problems with swallowing or vocalisation. Six out of the 8 animals survived to the planned termination date; 2 animals were terminated due to mild stenosis and deep tissue abscess formation, respectively. Human epithelial cells from mucosal brushings could only be identified at Weeks 1 and 4. The explanted tissue showed complete epithelialisation of the mucosal surface and the development of rudimentary vocal folds. However, there was no evidence of cartilage remodelling at the relatively early censor point. Single stage partial laryngeal replacement is a safe surgical procedure. Replacement with a tissue engineered laryngeal graft as a single procedure is surgically feasible and results in appropriate mucosal coverage and rudimentary vocal fold development.