Binding affinity predictions with hybrid quantum-classical convolutional neural networks.

Central in drug design is the identification of biomolecules that uniquely and robustly bind to a target protein, while minimizing their interactions with others. Accordingly, precise binding affinity prediction, enabling the accurate selection of suitable candidates from an extensive pool of potential compounds, can greatly reduce the expenses associated to practical experimental protocols. In this respect, recent advances revealed that deep learning methods show superior performance compared to other traditional computational methods, especially with the advent of large datasets. These methods, however, are complex and very time-intensive, thus representing an important clear bottleneck for their development and practical application. In this context, the emerging realm of quantum machine learning holds promise for enhancing numerous classical machine learning algorithms. In this work, we take one step forward and present a hybrid quantum-classical convolutional neural network, which is able to reduce by 20% the complexity of the classical counterpart while still maintaining optimal performance in the predictions. Additionally, this results in a significant cost and time savings of up to 40% in the training stage, which means a substantial speed-up of the drug design process.

Characterization of patients admitted to specialized geriatric acute care hospital units with the German version of the Standardized Evaluation and Intervention for Seniors at Risk (SEISAR) screening-instrument: a cross-sectional study.

BACKGROUND: The Standardized Evaluation and Intervention for Seniors at Risk (SEISAR) screening tool records major geriatric problems, originally applied in the emergency department. Particularly, the distinction of compensated and uncompensated problems is an interesting and new approach. Therefore, we translated the SEISAR in German language and used it to characterize patients in specialized geriatric hospital wards in Germany and to gather initial experience regarding its usability and practicability. METHODS: The tool was translated by three independent specialists in geriatric medicine and backtranslated for quality-assurance by a non-medical English native speaker. In a second step, 8 acute care geriatric hospital departments used the translated version to characterize all consecutive patients admitted over a period of one month between December 2019 and May 2020 at time of admission. RESULTS: Most of the 756 patients (78%) lived in an own apartment or house prior to hospital admission. Participants had on average 4 compensated and 6 uncompensated problems, a Barthel-Index of 40 pts. on admission with a median increase of 15 points during hospital stay, and a median length of stay of 16 days in the geriatric hospital department. CONCLUSION: SEISAR is an interesting standardized brief comprehensive geriatric assessment tool for the identification of compensated and uncompensated health problems in older persons. The data of this study highlights the number, variability, and complexity of geriatric problems in patients treated in specialized acute care geriatric hospital wards in Germany. TRIAL REGISTRATION: German Clinical trial register (DRKS-ID: DRKS00031354 on 27.02.2023).

[The problem of vitamin B12 deficiency: relevance, diagnosis and targeted therapy (based on materials of an interdisciplinary expert council with international participation)]. / Problema defitsita vitamina B12: aktual'nost', diagnostika i targetnaya terapiya (po materialam mezhdistsiplinarnogo soveta ekspertov s mezhdunarodnym uchastiem).

Deficiency of vitamin B12 occurs much more often than it is commonly believed and leads to a wide range of various disorders, the emergence of primarily neurological manifestations, while there is a lack of awareness among clinicians in the field of its causes, nonspecific manifestations, diagnostic methods and effective therapy. The conference «The problem of vitamin B12 deficiency and the experience of use in Germany¼ was devoted to this urgent clinical problem, within the framework of which an interdisciplinary council of experts, at which the most pressing issues were considered, associated with B12 deficiency.

[COVID-19 in old age-The geriatric perspective]. / COVID-19 im Alter ­ Die geriatrische Perspektive.

Predominantly the older population is affected by a severe course of COVID-19. The mortality of hospitalized patients with COVID-19 above the age of 80 years is up to 54% in international studies. These observations indicate the necessity to highlight the geriatric perspective on this disease. The diagnostics and treatment of COVID-19 do not differ between younger and older patients but atypical symptoms should be expected more frequently in old age. Older subjects show an increased need for rehabilitation after COVID-19. Paradoxically, increasing rehabilitation demands go along with a reduced availability of geriatric rehabilitation options, the latter being a consequence of closure or downsizing of rehabilitation departments during the pandemic. In general, measures of isolation and quarantine should be diligently balanced as the health and emotional consequences of such measures may be severe in older persons. In light of the poor prognosis of older COVID-19 patients, advanced care planning becomes even more relevant. Caregivers and physicians should be encouraged to compose advanced care directives that also reflect the specific circumstances of COVID-19. Fortunately, current data suggest that the effectiveness of the vaccination with the mRNA-vaccines approved in Germany may be equally high in older compared to younger persons.

[Insufficient use of anticoagulants in geriatric in-patients with atrial fibrillation and flutter (corrected)]. / Hospitalisierte geriatrische Patienten mit Vorhofflimmern sind nicht ausreichend mit Antikoagulanzien behandelt.

INTRODUCTION: Anticoagulation for the prevention of cardioembolic events is highly effective, but largely underused in frail older patients with atrial fibrillation or flutter (AF). This study aimed at identifying characteristics associated with anticoagulation use or non-use and the most frequent complications of this therapy. METHODS: Hospitalized geriatric patients treated in a one-year interval were retrospectively studied for the presence of AF and use or non-use of anticoagulation. The risk of stroke and the indication for permanent anticoagulation were assessed using the CHA2DS2-VASc score. RESULTS: In 451 of 1167 hospitalized patients (38.6%) there was a clear indication for anticoagulation. The most frequent indication for anticoagulation was AF in 381 patients (84.5% of 451 patients). Of these 381 patients, a strong indication for anticoagulation, based on CHA2DS2-VASc score, was identified in 379 patients. Of these patients, 200 (52.8%) did and 179 (47.2%) patients did not receive anticoagulation. 153 patients (40.4%) received antiplatelet therapy. 26 patients (6.7%) received neither anticoagulants nor antiplatelet therapy. The most common reason for non-implementation of anticoagulation was a high risk of falls in 93 patients (52%) of 179 patients without antocoagulation. The most frequent complications of anticoagulation were small hemorrhages without serious consequences in 8 cases. 4 patients suffered from serious bleedings. CONCLUSION: Almost half of our geriatric population did not receive anticoagulation despite a clear indication. Antiplatelet therapy use was associated with anticoagulation non-use.

[The ageing immune system]. / Das alternde Immunsystem.

The aging of the immune system, also called immunosenescence, contributes to the increased morbidity and mortality from infections, autoimmune diseases and cancer as well as to the low efficacy of vaccination in elderly persons. Immunosenescence is characterized by a decrease in cell-mediated immune function and by reduced humoral immune responses caused by age-related changes in the innate immune system and age-dependent defects in T-and B-cell function. This paper gives an overview of the most important modifications in the different compartments of the immune system during the ageing process.

Laparoscopic management of ovarian benign masses.

PURPOSE: To determine whether the presence of normal ovarian tissue could assist in the diagnosis of large benign ovarian neoplasms in young females and in choosing the laparoscopic treatment. MATERIALS AND METHODS: A prospective study of 25 patients treated surgically for a cystic ovarian neoplasm measuring diameter more than ten cm or volume more than 500 ml and having normal ovarian tissue or ovarian crescent sign (OCS). Ultrasonography was performed at six weeks, then at three, six, nine, and 12 months postoperatively. RESULTS: The mean age of patients was 15.3 +/- 3.6 years, ranging between 6.5 and 19 years. The mean preoperative volume of the ovarian neoplasm was 1,686 +/- 1,380 cm3, ranging between 550 and 6,000 cm3. The presence of OCS was visualized by ultrasonography in all 25 patients and serum tumor markers were negative in 22. No borderline tumors or malignancies were identified. There was a statistically significant difference between the volume of the affected ovary and the contralateral ovary during the first six weeks follow-up, but without significant difference after three months. CONCLUSIONS: Postoperative ultrasound revealed that the affected ovary resumed its normal volume within three months after surgery, despite the thinned appearance of the ovarian cortex present on ultrasound as the OCS. Laparoscopic ovarian preservation should be the preferred surgical approach for adolescents to ensure the conservation of the entire ovarian tissue.

Ovary-preserving tumorectomy for immature teratoma in an adolescent--case report.

The authors present a case of a 14-year-old premenarchal girl with a large solid tumor of the left ovary. The rim of normal ovarian tissue was visible around the tumor on ultrasonography scan. Although the levels of two tumor markers, LDH and CA125, were elevated, the authors performed an organ-sparing tumorectomy. The final pathology report revealed foci of immature neural tissue, with a final diagnosis immature teratoma Stage Ia.

Doppler parameters of maternal renal blood flow in normal pregnancy.

UNLABELLED: The purpose of this investigation was to evaluate changes in maternal renal arterial blood flow during pregnancy. MATERIALS AND METHODS: The study included 40 non-pregnant, 200 pregnant, and 30 women after delivery. The authors measured pulsatility index (Pi) and resistance index (Ri) in the right and left renal arteries in the hilus. The authors compared the values between non-pregnant and women during first, second, and third trimester and post-partum period and tested correlation with gestational age. RESULTS: The authors did not find a statistical difference in Pi and Ri between the right and left kidneys. There was no difference in Pi and Ri in pregnancy trimester compared to the non-pregnant state. There was no correlation between the values of Pi and Ri and gestational weeks. CONCLUSION: During pregnancy there are no changes in the values of maternal renal Pi and renal Ri. Unchanged total vascular resistance may result from physiological changes of the glomerular filtration rate.

Cerebrospinal fluid findings in geriatric patients from 2008 to 2011.

BACKGROUND: The chemical composition of the cerebrospinal fluid (CSF) is age-dependent. METHODS: Routine CSF parameters, the indications for lumbar puncture (LP), and the most frequent complications were retrospectively studied in patients older (n = 167) and younger (n = 36) than 65 years. RESULTS: In the absence of meningeal inflammation, the mean CSF lactate level of patients older than 65 years was slightly but significantly higher than the mean CSF lactate level of younger patients. The lactate level of patients with otherwise normal CSF findings correlated significantly with the age of the patients. In the absence of meningeal inflammation, the CSF-to-serum albumin ratio (QAlbumin) was significantly higher in older patients than in younger ones. The most frequent indication for LP, suspected infection of the central nervous system (CNS) (n = 110), was confirmed in 12.7% of patients. The only LP complication documented was headache in two patients. CONCLUSIONS: Elevations of QAlbumin and CSF lactate levels appear to be nonspecific findings in elderly patients. Suspected infections, the most frequent indication for LP, were confirmed by CSF analysis in more than 10% of patients. The very low complication rate of LP makes it a very valuable tool in the diagnostic routine for older patients with CNS diseases.

Distributed, limbic gray matter atrophy in patients after bacterial meningitis.

BACKGROUND AND PURPOSE: The structural basis of cognitive sequelae after bacterial meningitis in humans is still poorly understood. In animal models and human autopsy cases, neuronal apoptosis of the hippocampal formation in particular seems to play an important role. Here, we aimed to analyze if BM entails MR imaging structural consequences in humans in vivo. MATERIALS AND METHODS: We applied voxel-based morphometry in a cohort of BM survivors with normal conventional MR imaging after resolution of the acute inflammation to assess morphologic differences. RESULTS: We found clear gray matter volume loss in the limbic system including the hippocampal formation, thalamus, and cingulate gyri bilaterally as well as in the temporal lobe. These results were corroborated by an alternative atlas-based method. CONCLUSIONS: Even in patients with normal routine MR imaging results, clear-cut gray matter atrophy with a mesial temporal/limbic pattern was evident. The anatomic distribution is compatible with the neuropsychological deficit commonly observed in patients after BM. The similarity of the observed atrophy may point to causal link between BM and mesial temporal epilepsy.

Evaluation of utero-ovarian hemodynamics in relation to fertility and stage of endometriosis.

OBJECTIVE: The aim of this study was to compare hemodynamic changes in the uterine and ovarian arteries between infertile women with moderate and/or severe endometriosis and healthy women. In this prospective study, 99 women in their generative age were subjected to color Doppler ultrasonography to measure hemodynamic parameters from July 2010 to January 2011. The examination was performed during the proliferative or ovulatory phase of the natural menstrual cycle in a random sample of 54 women treated for endometriosis-induced infertility and 45 healthy women were included in control examination procedure. Irrespective of considered stage, endometriosis was most often found in the ovaries, in the sacro-uterine ligaments, peritoneum, and rectovaginally. Resistance to blood flow expressed as the resistance index (RI) in the measured arteries, was significantly higher in severe endometriosis compared to moderate form. Average values of pulsation index (PI) and RI are significantly higher, in both endometriosis stages, compared to measured values in healthy women.

The diagnostic spectrum in patients with suspected chronic Lyme neuroborreliosis--the experience from one year of a university hospital's Lyme neuroborreliosis outpatients clinic.

BACKGROUND AND PURPOSE: Studies addressing the diagnostic relevance of anti-Borrelia burgdorferi (BB) serum antibodies in patients with non-specific symptoms and suspected chronic Lyme neuroborreliosis (LNB) are scarce. METHODS: In this study, we enrolled within 1 year 122 patients with suspected chronic LNB. One hundred and fourteen patients had previously tested positive for BB. All patients had previously received antibiotic treatment. Each patient received a clinical examination and measurement of BB-specific antibodies. The diagnosis of neuroborreliosis was made according to the national guidelines of the German Society of Neurology. Nine patients had acute borreliosis. One of the nine met the criteria of acute LNB. Of the remaining 113 patients, 85 patients underwent a lumbar puncture. Ten seronegative subjects without lumbar puncture were also considered. In 61.8% of these 95 patients the quality of life, of sleep, mood, and anxiety were assessed. RESULTS: Of 95 patients, 25.3% had symptoms without a somatic cause or evidence of borreliosis, 38.9% had a well-defined illness unrelated to BB infection, and 29.5% suffered from symptoms without a detectable somatic cause, displaying antibodies against BB. Six patients were grouped as post-LNB syndrome. Most common symptoms in all categories were arthralgia, myalgia, dysaesthesia, depressive mood and chronic fatigue. CONCLUSION: Patients with persistent symptoms with elevated serum antibodies against BB but without signs of cerebrospinal fluid inflammation require further diagnostic examinations to exclude ongoing infection and to avoid co-infections and other treatable conditions (e.g. autoimmune diseases). One patient with acute LNB, who was treated with ceftriaxone for 3 weeks suffered from LNB with new headaches and persistent symptoms 6 months later. These data should encourage further studies with new experimental parameters.

Frequency of ovarian endometriosis in epithelial ovarian cancer patients.

PURPOSE: The aim of this study was to determine the frequency of endometriosis in epithelial ovarian cancer patients. METHODS: Patients who had undergone epithelial ovarian cancer surgery between 2000 and 2004 were subjected to a retrospective analysis. The analysis focused on the presence of ovarian endometriosis, histological types and stages of ovarian cancer, treatment types and five-year survival rate. RESULTS: Out of the 210 operated ovarian cancer patients, 23 had coexisting ovarian endometriosis. Ovarian endometriosis was detected in 3.5% (4 of 113 patients) of cases with serous ovarian cancer, in 31.6% (12 of 38 patients) of cases with endometrioid, and in 36.8% (7 of 19 patients) of cases with clear cell ovarian cancer. The treatment of ovarian cancer patients was a combination of surgery and chemotherapy. CONCLUSION: Endometriosis was most frequently present in patients with clear cell (36.8%) and endometrioid ovarian cancers (31.6%). The five-year survival rate for ovarian cancer patients in all stages was 39.1%.

S100B in the cerebrospinal fluid--a marker for glial damage in the rabbit model of pneumococcal meningitis.

The rabbit model provides an important experimental setting for the evaluation of antibiotic agents against pneumococcal meningitis. One of the primary targets of this model is the study of neuronal and glial cell damage in bacterial meningitis. The aim of this investigation was to evaluate whether a significant increase of S100B in the cerebrospinal fluid (CSF) as an indicator of white matter damage could be observed in this meningitis model. Seven rabbits were infected intracisternally with S. pneumoniae, and CSF S100B concentrations were examined serially before infection, at 12h, 14h, 17h, 20h, and at 24h after infection. The course of CSF S100B increase and its relation to other parameters of brain tissue destruction and CSF inflammation were measured. Axonal damage was visualized by amyloid precursor protein (APP) immunostaining and demyelination by Luxol Fast Blue/Periodic Acid Schiff (LFB-PAS) stain. In each animal, we observed a distinct rise in S100B concentration in the CSF due to pneumococcal meningitis. We conclude that the CSF concentration of the glial S100B protein can be used as an additional parameter for future interventional studies focusing on glial cell damage in the rabbit model of bacterial meningitis.

Value of ultrasonographic detection of normal ovarian tissue in the differential diagnosis of adnexal masses in pediatric patients.

OBJECTIVE: The aim of the study was to evaluate whether the presence of normal ovarian tissue, the 'ovarian crescent sign' (OCS), could assist in the differential diagnosis between benign and malignant adnexal masses in young patients. METHODS: This was a prospective observational study, from March 2004 to January 2006, which included 98 patients younger than 20 years of age (including two with bilateral tumors) with an ultrasonographic diagnosis of an adnexal mass. Morphological assessment using the Ueland index was performed in each case. Patients were also systematically examined for the presence of the OCS and a comparison was made with the Ueland index. All findings in surgically treated patients were compared with the final histological diagnosis. RESULTS: There were 100 adnexal masses: 90 were benign and 10 were malignant. Forty-eight were managed expectantly and 52, including 17 cases of adnexal torsion, underwent surgical treatment. The OCS was found in 65 (72%) benign adnexal masses and in one (10%) non-invasive malignant tumor. A Ueland index score of < 7 was found in 85 (94%) benign masses and in one (10%) non-invasive malignancy. The OCS was seen in 15 (45%) of 33 masses in premenarchal patients and in 51 (76%) of 67 masses in postmenarchal patients. The OCS was absent in 15 (88%) of the torsioned adnexal masses. CONCLUSIONS: The presence of normal ovarian tissue adjacent to an ovarian mass is a useful morphological feature that can assist exclusion of a malignant tumor in pediatric and adolescent patients. When compared with the Ueland index, diagnostic sensitivity of the OCS is similar, but specificity is lower. The presence of the OCS is significantly less frequent in premenarchal patients than in postmenarchal patients.

Primary double invasive cervical carcinoma, squamous cell carcinoma and adenocarcinoma--case report.

A case of 56-year old women with double primary invasive cervical carcinoma, squamous cell carcinoma and endometrioid adenocarcinoma is presented. The patient was subjected to radical abdominal hysterectomy with pelvic and paraaortic lymphadenectomy. Surgery was followed by radiotherapy. Since the treatment the patient has been doing well and is free of any signs of relapse of the disease.

Leiomyosarcoma of the uterine corpus with ovarian metastases in a 28-year-old woman: case report.

A case of invasive leiomyosarcoma of the uterine corpus with right ovarian metastases in a 28-year-old woman is presented. The patient was submitted to surgery including total abdominal hysterectomy with left salpingo-oophorectomy, dissection of the pelvic and paraaortal lymph nodes and fixation of the right ovary to the psoas muscle. Postoperative radiation therapy was applied. A year after treatment, the patient was well.