The role of research competence as an influencing factor for the careers of young academics. Findings and implications from studies on doctorates in medicine and life sciences in Germany.

Background: When viewed internationally, Germany boasts a high rate of doctoral candidates. Fields such as medicine and life sciences have a notably high proportion of doctoral students, a trend rooted in historical factors. Despite this, comprehensive empirical studies concerning the doctoral phase and early-career researchers, especially in relation to the rise of structured doctoral programmes, have only recently gained traction. Methods: We present findings from a project investigating young scientists in medicine and life sciences. Postdoctoral graduates from these disciplines were examined both quantitatively and qualitatively within the E-Prom projects, emphasizing the primary domain of research. Results: Our analysis indicates some benefits of structured doctoral programmes over traditional individual doctorates. However, the disparities between these doctoral approaches are less pronounced than anticipated. We also identified discrepancies between the programme descriptions and their actual execution. Integration into the scientific community and research-related self-efficacy are potential indicators of publication output and inclination towards a scientific career. Physicians exhibited lower research-related self-efficacy and a lesser tendency towards a scientific career than biologists. Notably, we found gender disparities disadvantaging female graduates, with these disparities being more marked in medicine. Conclusions: There is evidence to suggest that official representations of structured doctoral programmes do not always align with their practical applications, limiting their potential effectiveness. Therefore, resources should be allocated to ensure the consistent execution of these programmes. Given the empirical evidence supporting the benefits of community integration for junior researchers, efforts should be made to facilitate their networking. Additionally, our findings emphasize the necessity of providing enhanced support for young female scientists.

Clinical variety and prognosis of intracranial arachnoid cysts in children.

Arachnoid cysts (AC) occur in different intracranial locations. Management and prognosis depend on the clinical presentation and treatment guidelines do not exist. With this study, we want to demonstrate the clinical variety of arachnoid cysts in children and place a focus on outcome factors in operated cases. This retrospective study of a consecutive single unit series of children, who underwent AC surgery between January 2010 and September 2019, provides demographic, clinical, imaging data, and information about surgical treatment and outcome. Overall, 63 patients (71.4 male) underwent surgery. Mean age was 50 months (0-191). Mean follow-up was 40 months (0-121). Eighty-one percent of patients presented with symptoms/signs of raised ICP. Focal neurological deficits were present in 15.9%, headache in 11.1% of children. Galassi cysts represented the predominant type (30.2%), followed by suprasellar (14.3%), quadrigeminal (12.7%), retrocerebellar, CPA and midline (each 11.1%), and hemispheric cysts (7.9%). Endoscopic and microsurgical fenestrations were performed in 27% and 58.7%, stent or shunt insertion in 6.3%/57.9% of the cases. In 33.3% of the cases one and in 12.7%, a second reintervention became necessary. Reoperation rate was significantly higher in children < 1 year (p = 0.003). Cyst volume decreased in 85.7%. Seventy percent of the patients were symptom free, 5% suffered from headache, and 22% from developmental disorders. All focal neurological symptoms resolved. Complication rate and outcome are depending on age and cyst location. Recurrence and revision rates are significantly higher in young infants (p = 0.003). Midline cysts with CCA are associated with developmental disorders.

Dual PARP and RAD51 Inhibitory Drug Conjugates Show Synergistic and Selective Effects on Breast Cancer Cells.

The genetic principle of synthetic lethality has most successfully been exploited in therapies engaging Poly-ADP-ribose-polymerase (PARP) inhibitors to treat patients with homologous recombination (HR)-defective tumors. In this work, we went a step further following the idea of a local molecular cooperation and designed hybrid compounds M1-M3. The drug conjugates M1-M3 combine Olaparib, the first PARP inhibitor approved for clinical use, with Cpd 1, an inhibitor of RAD51 that blocks its HR functions and yet permits RAD51 nucleoprotein filament formation on single-stranded DNA. While in M2 and M3, the parental drugs are linked by -CO-(CH2)n-CO-spacers (n = 2 and 4, respectively), they are directly merged omitting the piperazine ring of Olaparib in M1. Monitoring anti-survival effects of M1-M3 in six breast cancer cell lines of different molecular subtypes showed that in each cell line, at least one of the drug conjugates decreased viability by one to two orders of magnitude compared with parental drugs. While triple-negative breast cancer (TNBC) cells with frequent BRCA1 pathway dysfunction were sensitive to spacer-linked hybrid compounds M1 and M2 regardless of their HR capacities, non-TNBC cells were responsive to the merged drug conjugate M1 only, suggesting different spatial requirements for dual inhibition in these two groups of cell lines. These results demonstrate that, depending on chemical linkage, dual PARP1-RAD51 inhibitory drugs can either sensitize non-TNBC and re-sensitize TNBC cells, or discriminate between these groups of cells.

A Fibrinogen Alpha Fragment Mitigates Chemotherapy-Induced MLL Rearrangements.

Rearrangements in the Mixed Lineage Leukemia breakpoint cluster region (MLLbcr) are frequently involved in therapy-induced leukemia, a severe side effect of anti-cancer therapies. Previous work unraveled Endonuclease G as the critical nuclease causing initial breakage in the MLLbcr in response to different types of chemotherapeutic treatment. To identify peptides protecting against therapy-induced leukemia, we screened a hemofiltrate-derived peptide library by use of an enhanced green fluorescent protein (EGFP)-based chromosomal reporter of MLLbcr rearrangements. Chromatographic purification of one active fraction and subsequent mass spectrometry allowed to isolate a C-terminal 27-mer of fibrinogen α encompassing amino acids 603 to 629. The chemically synthesized peptide, termed Fα27, inhibited MLLbcr rearrangements in immortalized hematopoietic cells following treatment with the cytostatics etoposide or doxorubicin. We also provide evidence for protection of primary human hematopoietic stem and progenitor cells from therapy-induced MLLbcr breakage. Of note, fibrinogen has been described to activate toll-like receptor 4 (TLR4). Dissecting the Fα27 mode-of action revealed association of the peptide with TLR4 in an antagonistic fashion affecting downstream NFκB signaling and pro-inflammatory cytokine production. In conclusion, we identified a hemofiltrate-derived peptide inhibitor of the genome destabilizing events causing secondary leukemia in patients undergoing chemotherapy.

The lonely struggle with autonomy: A case study of first-year university students' experiences during emergency online teaching.

This paper explores how first-year students experienced emergency online teaching during COVID-19 and aims at understanding individual experiences related to basic psychological need satisfaction, considering different levels of contextual facilitators for learning activities involving technology in higher education derived from the C-flat model. Employing a case study approach, interviews of 15 chemistry students were qualitatively analyzed. The results show negative effects of lacking internet connectivity and concurrence of learning and home spaces but positive effects of ceased commute between home and campus. Teachers' implementation of digital learning opportunities was perceived as adequate but did not sufficiently address the overwhelming increase in students' autonomy and decrease in social relatedness. Students' self-regulation skills as well as skills to initiate and maintain social contacts for interactive learning activities and for motivational support emerged as crucial aspects. Many students were not able to cope appropriately and students' need satisfaction during emergency online teaching appeared to be related to students' prior need satisfaction resulting in five groups of students, with two being relatively resilient and three being vulnerable to the disruptions of regular onsite teaching. Implications for further research and practice are discussed.

Regulations and practices of structured doctoral education in the life sciences in Germany.

Structured doctoral education is increasingly preferred compared to the individual model. Several science policy organisations give recommendations on how to structure doctoral education. However, there is little research on to what extent these recommendations find their way into practice. In our study, we first compared European and German recommendations on doctoral education with, second, the institutional regulations of structured doctoral programmes (N = 98) in the life sciences at twelve different German universities. Additionally, we third asked doctoral graduates (N = 1796) of these structured doctoral programmes and graduates of individual doctoral studies about their experience in doctoral education. Fourth, we contrasted the regulations of structured doctoral programmes with the reported experiences of their graduates. We found significant deviations of the reported practices of graduates from the regulations of their organisations, regarding the student admission, supervision and curricular activities of doctoral candidates. The efficacy of structured versus traditional doctoral education should be examined based on reported practice rather than on the respective written regulations.

Functional impairment after successful surgical reconstruction for proximal hamstring avulsion.

PURPOSE: Surgical refixation procedures after hamstring avulsion injuries show satisfying to excellent outcome results. However, for post-operative evaluation so far, used outcome scores were partially not injury-specific, heterogeneous, difficult to compare, and possibly overestimated due to ceiling effects. A new injury-specific assessment tool has recently been published, potentially depicting more realistic outcome results. Thus, the aim of our study was to evaluate patients after hamstring refixation surgery using previously utilized as well as the new Perth hamstring assessment tool (PHAT). METHODS: A series of operated hamstring injuries were retrospectively evaluated using the PHAT as well as the widespread, customized Lower Extremity Functional Scale (C-LEFS) and the customized Marx score (C-Marx). Scores as well as potential ceiling effects were evaluated individually, and compared and correlated to each other. RESULTS: Sixty-four patients were enrolled into the survey. Forty-nine questionnaires (76%) could be evaluated. The mean total PHAT score (0-100) after 28 months (SD ± 17.0) was 74.1 (SD ± 22.5) points. Mean total C-LEFS (0-80) revealed 61.4 (SD ± 18.1) points, and the mean total C-Marx score (20) was 19.4 (SD ± 1.6) points. Pearson's correlation between the individual questionnaires was high between the PHAT and the C-LEFS (r = 0.81) and low between the PHAT and C-Marx (r = 0.52) and between C-LEFS and C-Marx (r = 0.48). CONCLUSION: The presented study confirms good subjective functional outcomes after surgical intervention of hamstring avulsions in all scores. Nevertheless, using the PHAT, residual complaints are more common than often described in previous studies interpreting "conventional" scores. For future decision and patient guidance, more studies using injury-specific assessments such as the PHAT in combination with objective measurements are eligible.

[Surgical Refixation after Proximal Hamstring Tendon Avulsion Injuries: Does the Time of Surgery Influence Functional Outcomes?] / Operative Refixation bei proximalem Hamstringabriss: Ist der OP-Zeitpunkt relevant für das funktionelle Outcome?

Background Proximal hamstring tendon avulsion injuries are rare. If they do occur, surgical treatment with tendon refixation is regarded as the method of choice. Surgical outcome measurements have been investigated heterogeneously and, therefore, are difficult to compare. Hence, the possibility for correlations between postoperative outcomes and surgical methods or time of surgery is limited. Objective Using the new, validated and injury-specific Perth Hamstring Assessment Tool (PHAT), we aimed to investigate a population of own patients in order to compare the results in relation to the time of surgery after trauma. Methods In this retrospective case control study, all patients who had undergone hamstring avulsion surgery between 1/2011 and 3/2016 with a follow-up period of at least six months were asked to document their subjective functional outcome using the PHAT. Depending on the time of surgery after trauma, patients and the results of their questionnaires were assigned either to an acute (< 4 weeks), a delayed (1 - 3 months) or a chronic (> 3 months) group. Results In the named period, 64 patients had a hamstring refixation surgery, 57 of them could be included in the study. 39 (68 %) returned the completed PHAT questionnaire. The mean PHAT score (0 - 100 pts.) was 72.4 (SD ±â€Š21.0). There was no significant difference between the acute and the delayed group (77.0 ±â€Š22.0 vs. 63.4 ±â€Š16.2; p: 0.0673), whereas a significant difference was detected between the acute and the chronic group (77.0 ±â€Š22.0 vs. 58.3 ±â€Š20.2; p: 0.0214). Conclusion The results of this study show that an early diagnosis and subsequent operation of a hamstring tendon avulsion injury leads to significant better functional outcomes compared with chronic procedures.

Receptors for short-chain fatty acids in brush cells at the "gastric groove".

In the stomach of rodents clusters of brush cells are arranged at the "gastric groove," immediately at the transition zone from the non-glandular reservoir compartment to the glandular digestive compartment. Based on their taste cell-like molecular phenotype it has been speculated that the cells may be capable to sense constituents of the ingested food, however, searches for nutrient receptors have not been successful. In this study, it was hypothesized that the cells may express receptors for short-chain fatty acids, metabolites generated by microorganisms during the storage of ingested food in the murine forestomach, which lacks the acidic milieu of more posterior regions of the stomach and is colonized with numerous microbiota. Experimental approaches, including RT-PCR analysis and immunohistochemical studies, revealed that the majority of these brush cells express the G-protein coupled receptor types GPR41 (FFAR3) and GPR43 (FFAR2), which are activated by short-chain fatty acids. Both, the GPR41 receptor proteins as well as an appropriate G-protein, α-gustducin, were found to be segregated at the apical brush border of the cells, indicating a direct contact with the luminal content of this gastric region. The exposure of microvillar processes with appropriate receptors and signaling elements to the gastric lumen suggests that the brush cells may in fact be capable to sense the short-chain fatty acids which originate from fermentation processes during the retention of ingested food in the anterior part of the stomach.

Putative interaction of brush cells with bicarbonate secreting cells in the proximal corpus mucosa.

The gastric epithelium is protected from the highly acidic luminal content by alkaline mucus which is secreted from specialized epithelial cells. In the stomach of mice strong secretion of alkaline fluid was observed at the "gastric groove," the border between corpus and fundus mucosa. Since this region is characterized by numerous brush cells it was proposed that these cells might secrete alkaline solution as suggested for brush cells in the bile duct. In fact, it was found that in this region multiple cells express elements which are relevant for the secretion of bicarbonate, including carbonic anhydrase (CAII), the cystic fibrosis transmembrane conductance regulator (CFTR) and the Na(+)/H(+) exchanger (NHE1). However, this cell population was distinct from brush cells which express the TRP-channel TRPM5 and are considered as putative sensory cells. The location of both cell populations in close proximity implies the possibility for a paracrine interaction. This view was substantiated by the finding that brush cells express prostaglandin synthase-1 (COX-1) and the neighboring cells a specific receptor type for prostaglandins. The notion that brush cells may be able to sense a local acidification was supported by the observation that they express the channel PKD1L3 which contributes to the acid responsiveness of gustatory sensory cells. The results support the concept that brush cells may sense the luminal content and influence via prostaglandins the secretion of alkaline solution.

Parathyroidectomy, elevated depression scores, and suicidal ideation in patients with primary hyperparathyroidism: results of a prospective multicenter study.

OBJECTIVE: To assess anxiety and depression symptoms, suicidal ideation, and health-related quality of life (HRQOL) in a large series of consecutive patients with primary hyperparathyroidism (pHPT) before and after parathyroidectomy. DESIGN: This prospective multicenter study investigated preoperative and postoperative depression, anxiety, suicidal ideation, and HRQOL in patients with pHPT and compared these variables with a control group with nontoxic thyroid nodules. PATIENTS: The study included 194 patients with pHPT and 186 control subjects. MAIN OUTCOME MEASURES: Depression was evaluated with the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire-9, which also assessed suicidal ideation. Anxiety was evaluated with the HADS. Health-related quality of life was measured with the 36-Item Short Form survey. RESULTS: Parathyroidectomy achieved a 98% cure rate. Preoperatively, severe depression (HADS score ≥ 11) was seen in 20% of the pHPT group and 9% of the control group. The Patient Health Questionnaire-9 detected moderate to severe depression in 17% of the patients with pHPT and 7% of the control subjects. Patients with pHPT had higher HADS anxiety scores (mean, 7.7) than control subjects (P < .01) or the German normative sample (P < .001). Compared with control subjects, patients with pHPT had significantly lower 36-Item Short Form survey preoperative physical and mental health summary scores (42.7 vs 49.5 and 41.2 vs 46.8, respectively; P = .001 for both comparisons). At 12 months follow-up, depression and anxiety decreased significantly in patients with pHPT; the prevalence of suicidal ideation was more than halved from the baseline (10.7% vs 22%; P = .008). Both physical and mental health scores (45.7 and 47.7, respectively) improved in patients with pHPT (P < .001 each) but not in control subjects. CONCLUSIONS: Depression, anxiety, and decreased HRQOL appear to be related to pHPT. Successful parathyroidectomy seems to reduce psychopathologic symptoms and improve HRQOL in this setting.

Band-like arrangement of taste-like sensory cells at the gastric groove: evidence for paracrine communication.

The discovery of taste-related elements within the gastrointestinal tract has led to a growing interest in the mechanisms and physiological significance of chemosensory monitoring of chymus composition. Previous work suggests that brush cells located in the "gastric groove," which parallels the "limiting ridge," a structure in rodents that divides the fundus from the corpus, are candidate sensory cells. A novel sectioning technique revealed that these cells are arranged in a palisade-like manner forming a band which borders the whole length of the corpus epithelium. Using transgenic PLCß2 promoter-GFP mice and specific antibodies, we have demonstrated that most of these cells express gustducin, PLCß2, and TRPM5; typical signaling proteins of gustatory sensory "type II" cells. These molecular features strongly suggest that the cells may be capable of sensing nutrient or non-nutrient constituents of the ingested food. Since there is no evidence that brush cells are endocrine cells, attempts were made to explore how such putative chemosensory cells might transmit the information to "effector" cells. It was found that most of the cells express the neuronal nitric oxide synthase (NOS) suggesting some paracrine interaction with adjacent cells. Moreover, they also express choline acetyltransferase (ChAT) as well as the vesicular protein SNAP25, indicating the potential for cholinergic transmission, possibly with subjacent enteric nerve fibers.

The use of high-resolution ultrasonography for preoperative detection of metastases in sentinel lymph nodes of patients with cutaneous melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) reliably assesses the status of the regional lymph node basins and provides prognostic information in patients with cutaneous melanoma, but is logistically demanding and expensive. OBJECTIVE: The aim of this study was to evaluate the ability of high resolution B-mode ultrasonography (US) for pre-operative identification and characterization of sentinel lymph nodes (SLN) in patients with cutaneous melanoma. PATIENTS AND METHODS: In a prospective trial, the use of high resolution US was assessed in 25 consecutive patients with cutaneous melanoma identified for SLNB, first, for its value in primary detection of SLN, and, second, for its value in the correct assessment of SLN after lymphoscintigraphic mapping. RESULTS: High resolution B-mode US correctly identified two of 6 positive SLN. The sensitivity, specificity, positive predictive value, and negative predictive value of US were 33.3% (95% CI 43.3-77.7), 100.0% (95% CI 88.1-100.0), 100.0% (95%CI 15.8-100.0) and 87.9% (95% CI 71.8-96.6), respectively. CONCLUSION: High resolution B-mode US cannot replace SLNB, especially in the detection of micrometastases, but it remains the most important method to assess the lymph node status for macrometastases presurgically.

Ultrasound mapping of lymph node and subcutaneous metastases in patients with cutaneous melanoma: results of a prospective multicenter study.

BACKGROUND: Ultrasound (sonography, B-mode sonography, ultrasonography) examination improves the sensitivity in more than 25% compared to the clinical palpation, especially after surgery on the regional lymph node area. OBJECTIVE: To evaluate the distribution of metastases during follow-up in the draining lymph node areas from the scar of primary to regional lymph nodes (head and neck, supraclavicular, axilla, infraclavicular, groin) in patients with cutaneous melanoma with or without sentinel lymph node biopsy (SLNB) or former elective or consecutive complete lymph node dissection in case of positive sentinel lymph node (CLND). cv: Prospective multicenter study of the Departments of Dermatology of the Universities of Homburg/Saar, Tubingen and Munich (Germany) in which the distribution of lymph node and subcutaneous metastases were mapped from the scar of primary to the lymphatic drainage region in 53 melanoma patients (23 women, 30 men; median age: 64 years; median tumor thickness: 1.99 mm) with known primary, visible lymph nodes or subcutaneous metastases proven by ultrasound and histopathology during the follow-up. RESULTS: Especially in the axilla, infraclavicular region and groin the metastases were not limited to the anatomic lymph node regions. In 5 patients (9.4%) (4 of them were in stage IV) lymph node metastases were not located in the corresponding lymph node area. 32 patients without former SLNB had a time range between melanoma excision and lymph node metastases of 31 months (median), 21 patients with SLNB had 18 months (p < 0.005). In 11 patients with positive SLNB the time range was 17 months, in 10 patients with negative SLNB 21 months (p < 0.005); in 32 patients with CLND the time range was 31 months and in 21 patients without CLND 18 months (p<0.005). In thinner melanomas lymph node metastases occurred later (p<0.05). CONCLUSIONS: After surgery of cutaneous melanoma, SLNB and CLND the lymphatic drainage can show significant changes which should be considered in clinical and ultrasound follow-up examinations. Especially for high-risk melanoma patients follow-up examinations should be performed at intervals of 3 months in the first years. Patients at stage IV should be examined in all regional lynph node areas clinically and by ultrasound.

Lymph node metastases in patients with cutaneous melanoma: improvements in diagnosis by signal-enhanced color Doppler sonography.

The purpose of the study was to evaluate whether signal-enhanced color Doppler sonography (CDS) is superior to native CDS in detection of characteristic vascularity patterns that are important for the differentiation between benign and malignant lymphadenopathy in patients with cutaneous melanomas. Twenty-two melanoma patients presenting with 24 structures suspicious for metastases in B-Mode sonography were examined using native and signal-enhanced CDS in a prospective two-center study. Presumptive sonographic diagnoses were compared with results of histopathological and follow-up examinations. Signal-enhanced CDS gave additional information about vascularization of lymph node metastases and reactive lymph nodes, which was indicative for the differential diagnosis in 12 of 24 examinations. For lymph node metastases, signal enhancement improved the visualization of accessory peripheral vessels in four of 10 examinations. Concerning reactive lymph nodes, hilar vessels in part with branching to the lymph node periphery could be better identified after application of the contrast enhancer in eight of 13 examinations. Signal-enhanced CDS is demonstrated as an important additional diagnostic tool for improved differentiation between malignant and reactive lymph nodes and may be of special value in preventing unnecessary lymphadenectomy in small reactive lymph nodes.