Genetic analyses of ancient tea trees provide insights into the breeding history and dissemination of Chinese Assam tea (Camellia sinensis var. assamica).

Chinese Assam tea (Camellia sinensis var. assamica) is an important tea crop with a long history of cultivation in Yunnan, China. Despite its potential value as a genetic resource, its genetic diversity and domestication/breeding history remain unclear. To address this issue, we genotyped 469 ancient tea plant trees representing 26 C. sinensis var. assamica populations, plus two of its wild relatives (six and three populations of C. taliensis and C. crassicolumna, respectively) using 16 nuclear microsatellite loci. Results showed that Chinese Assam tea has a relatively high, but comparatively lower gene diversity (HS = 0.638) than the wild relative C. crassicolumna (HS = 0.658). Clustering in STRUCTURE indicated that Chinese Assam tea and its two wild relatives formed distinct genetic groups, with considerable interspecific introgression. The Chinese Assam tea accessions clustered into three gene pools, corresponding well with their geographic distribution. However, NewHybrids analysis indicated that 68.48% of ancient Chinese Assam tea plants from Xishuangbanna were genetic intermediates between the Puer and Lincang gene pools. In addition, 10% of the ancient Chinese Assam tea individuals were found to be hybrids between Chinese Assam tea and C. taliensis. Our results suggest that Chinese Assam tea was domesticated separately in three gene pools (Puer, Lincang and Xishuangbanna) in the Mekong River valley and that the hybrids were subsequently selected during the domestication process. Although the domestication history of Chinese Assam tea in southwestern Yunnan remains complex, our results will help to identify valuable genetic resources that may be useful in future tea breeding programs.

Patients with more complex ankle fractures are associated with poorer patient-reported outcome: an observational study of 11,733 patients from the Swedish Fracture Register.

BACKGROUND AND PURPOSE: Patient-reported outcome measures (PROMs) following ankle fractures, including all fracture types, have not been reported. It is therefore unclear whether fracture morphology correlates with outcome. We aimed to analyze PROMs in patients with an ankle fracture in relation to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification using population-based register data from the Swedish Fracture Register (SFR). METHODS: All patients aged ≥ 18 years with an ankle fracture (AO/OTA 44A1-C3) registered in the SFR between 2012 and 2019 were retrieved from the register. Patients with completed PROM questionnaires (Short Musculoskeletal Function Assessment and EuroQol-Visual Analogue Scale) on both day 0 (pre-trauma) and 1-year post-trauma were included. The difference in PROMs between day 0 and 1 year was calculated for each patient (delta value) and mean delta values were calculated at group level, based on the AO/OTA fracture classification. RESULTS: 11,733 patients with 11,751 fractures with complete PROMs were included. According to the AO/OTA classification, 21% were A fractures, 67% were B fractures and 12% were C fractures. All groups of patients, regardless of fracture class (A1-C3), displayed an impairment in PROMs after 1 year compared with day 0. Type C fractures displayed a larger impairment in PROMs at group level than type B, which in turn had a greater impairment than type A. The same pattern was seen in groups 3, 2, and 1 for A and B fractures. CONCLUSION: We found that the AO/OTA classification is prognostic, where more complex fractures were associated with poorer PROMs.

A leading-edge scenario in the phylogeography and evolutionary history of East Asian insular Taxus in Taiwan and the Philippines.

The cool temperate origin of gymnosperm Taxus species in East Asia is specifically diverse and widespread. Certain lineages have managed to extend their distribution further south to subtropical and tropical islands such as Taiwan and the Philippines. To address questions including whether these insular lineages, recently identified as T. phytonii, have become genetically distinct from each other and from their continental relatives, and when and how they colonized their residing islands, we sampled over 11 populations, covering 179 Taxus individuals from Taiwan and the Philippines. Using four cpDNA and one nuclear marker, we showed in population genetic and genealogical analyses that the two insular lineages were genetically distinct from each other and also from other continental Taxus and that they represented each other's closest relative. Estimated with the coalescent-based multi-type tree (MTT) analyses, we inferred an origin of Taiwanese T. phytonii more ancient than 2.49 Mya and that of Philippine T. phytonii more ancient than 1.08 Mya. In addition, the divergence demographic history revealed by both MTT and isolation with migration (IM) analyses indicated the presence of recent post-split migrations from a continental taxon, T. mairei, to Taiwanese T. phytonii, as well as from Taiwanese T. phytonii to Philippine T. phytonii. Overall, this study suggests Taiwan as a stepping stone through which the temperate-origin yew trees can extend their distributions to tropical regions such as the Philippines.

Home-Based Titration with Duodenal Infusion of Levodopa-Carbidopa Intestinal Gel in People with Parkinson's Disease: An Observational Feasibility Study.

Background: Testing and titration of the right levodopa equivalent dose are usually performed during a hospital admission. However, optimal dose titration in people with Parkinson's disease (PwPs) may depend on home environment, emotional stress, and physical activity of everyday life. Objective: Firstly, to evaluate the feasibility and safety of a home-based LCIG titration program and patients'/caregivers' satisfaction. Secondly, to identify barriers and facilitators for home-based titration. Method: This study assesses the feasibility and safety of home-based titration of levodopa duodenal infusions with the use of self-reported evaluation questionnaires with open-ended questions included, registration of total time used, and number of contacts/visits. A telemedicine solution was used to remotely monitor the patients, adjust treatment, and provide support and guidance to patients and caregivers. Results: Ten of 12 PwPs (5 females and 7 males) completed the total titration program. Eight of the 12 PwPs were dependent on help. These 8 PwPs also had a high burden of nonmotor symptoms (NMS). Cognitive impairments varied in severity (range 16-30). Time spent with home visits was on average 93.4 minutes (ranging from 35 to 180 minutes), and the length of the total titration (LCIG initiation to termination of titration) was on average 3.4 days with 2-5 (mean 3.2) contacts/visits with PD team members. The average score on the satisfaction evaluation questionnaires was lower in the caregiver group (mean 31.8) than the PwP outcome (mean 36.2). Conclusions: Telehealth-assisted home-based titration programs are feasible due to the length of the titration period, number of contacts, and time spent in PwPs' private homes, are rated satisfactory and safe by PwPs and caregivers, and may be a substitute for in-hospital treatment. Clinical recommendations including facilitators and barriers from a patient/caregiver perspective are displayed. This trial is registered with NCT4196647.

Sister Mary Joseph nodule.

Sister Mary Joseph nodule (SMJN) is a rare clinical finding in patients with metastatic adenocarcinoma. This is a case report of a 69-year-old man, who presented with a cutaneous element by his umbilicus at his GP. He was referred to a dermatologist, then a plastic surgeon. The element was a metastasis from adenocarcinoma originating from his caecum. It is important for doctors to know of SMJN as a rare presentation of metastatic cancer, and to clinically examine the patient for an abdominal starting point, when presented with a cutaneous tumour at the position of the umbilicus.

Reoperation-free survival after hip screws or hip arthroplasty for undisplaced femoral neck fractures in the elderly.

Aims: Our primary aim was to assess reoperation-free survival at one year after the index injury in patients aged ≥ 75 years treated with internal fixation (IF) or arthroplasty for undisplaced femoral neck fractures (uFNFs). Secondary outcomes were reoperations and mortality analyzed separately. Methods: We retrieved data on all patients aged ≥ 75 years with an uFNF registered in the Swedish Fracture Register from 2011 to 2018. The database was linked to the Swedish Arthroplasty Register and the National Patient Register to obtain information on comorbidity, mortality, and reoperations. Our primary outcome, reoperation, or death at one year was analyzed using restricted mean survival time, which gives the mean time to either event for each group separately. Results: Overall, 3,909 patients presenting with uFNFs were included. Of these patients, 3,604 were treated with IF and 305 with primary arthroplasty. There were no relevant differences in age, sex, or comorbidities between groups. In the IF group 58% received cannulated screws and 39% hook pins. In the arthroplasty group 81% were treated with hemiarthroplasty and 19% with total hip arthroplasty. At one year, 32% were dead or had been reoperated in both groups. The reoperation-free survival time over one year of follow-up was 288 days (95% confidence interval (CI) 284 to 292) in the IF group and 279 days (95% CI 264 to 295) in the arthroplasty group, with p = 0.305 for the difference. Mortality was 26% in the IF group and 31% in the arthroplasty group at one year. Reoperation rates were 7.1% in the IF group and 2.3% in the arthroplasty group. Conclusion: In older patients with a uFNF, reoperation-free survival at one year seems similar, regardless of whether IF or arthroplasty is the primary surgery. However, this comparison depends on the choice of follow-up time in that reoperations were more common after IF. In contrast, we found more early deaths after arthroplasty. Our study calls for a randomized trial comparing these two methods.

Severe lympho-depletion, abrogated thymopoiesis and systemic EBV positive T-cell lymphoma of childhood, a case.

Epstein-Barr virus (EBV) associated T-cell and NK-cell lymphoproliferative diseases are lethal and extremely rare in Caucasians. We expand on the clinical, immunological and histogenetic characteristics associated with this second European case (19 years old, previously healthy, Caucasian boy) of systemic EBV positive T-cell lymphoma of childhood. We report, as novel findings, severe lympho-depletion and abrogation of thymopoiesis secondary to severe EBV activation and excessive immune activation. Similar to the first European case, we also detected a somatic missense variant in the proto-oncogene FYN. In the first European patient however, the FYN variant allele frequency (VAF) was 10% and the patient only experienced moderate leukopenia, whereas in our case, the VAF was 48% and the patient experienced severe leukopenia and lymphopenia. This could suggest a pathogenic role of these FYN variants in driving excessive T cell activation. If confirmed, FYN might become target in future treatments of this fatal disorder.

Treatment and outcome of AO/OTA type C distal radius fractures: 12 199 fractures from the Swedish Fracture Register.

The aim of this study was to examine the epidemiology, treatment, and patient-reported outcome of AO/OTA type C distal radius fractures (DRF) using data from a large national fracture register. We used prospectively collected data from the Swedish Fracture Register covering all AO/OTA type C DRFs registered between April 2012 and December 2018. Data on fracture type, epidemiology, trauma-mechanism, and treatment had been recorded by the treating physician. Patients had been sent an outcome questionnaire including EQ-VAS, EQ-5D, and the SMFA at the time of injury and 12 months after. A total of 12 199 cases with AO/OTA type C fracture were identified. AO/OTA type C1 fracture was most common, with 5400 cases, followed by AO type C2 with 4304 and AO/OTA type C3 with 2495. Cast treatment and surgical treatment with volar locking plate fixation were the most common treatments. Patient-reported outcome measures worsened significantly one year after the fracture, and 56% reported moderate problems with pain and discomfort one year after the fracture. Patients treated with a volar plate reported a significantly larger deterioration in EQ-5D outcome compared to patients treated with a cast. No treatment method was found to be superior. A good outcome after a type C fracture is possible, but many patients do not recover completely. Our findings indicate a relatively better self-reported outcome for patients treated with a cast, but as treatment was not randomized the clinical relevance is unclear.

The different strategies in treating displaced femoral neck fractures: mid-term surgical outcome in a register-based cohort of 1,283 patients aged 60-69 years.

BACKGROUND AND PURPOSE: In patients around retirement age controversy exists as to whether to treat displaced femoral neck fracture (dFNF) with internal fixation (IF) or arthroplasty. An arthroplasty in this age group may need revision due to a long expected remaining lifetime. IF carries a higher risk of early failure but a maintained native hip if healing occurs. We aimed to determine the cumulative 5-year rate of conversion to arthroplasty after IF and implant revision after primary total hip arthroplasty (THA), respectively. PATIENTS AND METHODS: In this longitudinal cohort study, patients aged 60-69 years registered with a dFNF in the Swedish Fracture Register (SFR) 2012-2018 were cross-referenced with available data from the Swedish Arthroplasty Register (SAR) until December 31, 2019. Conversion to arthroplasty or revision were analyzed utilizing competing risk, with death as competing event. RESULTS: At 5 years, the cumulative rate of conversion to arthroplasty after IF was 31% (95% confidence interval [CI] 26-37). For primary THA, the 5-year rate of revision was 4.0% (CI 2.8-5.8). The 5-year mortality did not differ, being 20% (CI 16-27) and 23% (CI 20-28) after IF and THA, respectively. Regression analyses did not identify any risk factors for conversion arthroplasty based on the variables in the register. CONCLUSION: A follow-up of 5 years catches most reoperations after IF, resulting in a 31% conversion rate. The 4% revision rate at 5 years after primary THA should be seen as an intermediate result, as late complications may occur.

Phylogenetic Relationships and Next-Generation Barcodes in the Genus Torreya Reveal a High Proportion of Misidentified Cultivated Plants.

Accurate species identification is key to conservation and phylogenetic inference. Living plant collections from botanical gardens/arboretum are important resources for the purpose of scientific research, but the proportion of cultivated plant misidentification are un-tested using DNA barcodes. Here, we assembled the next-generation barcode (complete plastid genome and complete nrDNA cistron) and mitochondrial genes from genome skimming data of Torreya species with multiple accessions for each species to test the species discrimination and the misidentification proportion of cultivated plants used in Torreya studies. A total of 38 accessions were included for analyses, representing all nine recognized species of genus Torreya. The plastid phylogeny showed that all 21 wild samples formed species-specific clades, except T. jiulongshanensis. Disregarding this putative hybrid, seven recognized species sampled here were successfully discriminated by the plastid genome. Only the T. nucifera accessions grouped into two grades. The species identification rate of the nrDNA cistron was 62.5%. The Skmer analysis based on nuclear reads from genome skims showed promise for species identification with seven species discriminated. The proportion of misidentified cultivated plants from arboreta/botanical gardens was relatively high with four accessions (23.5%) representing three species. Interspecific relationships within Torreya were fully resolved with maximum support by plastomes, where Torreya jackii was on the earliest diverging branch, though sister to T. grandis in the nrDNA cistron tree, suggesting that this is likely a hybrid species between T. grandis and an extinct Torreya ancestor lineage. The findings here provide quantitative insights into the usage of cultivated samples for phylogenetic study.

Conservatively treated wound for four months turned out to be highly malignant cutaneous angiosarcoma.

Angiosarcomas are rare, highly malignant tumours of vascular origin. They present as fast growing, haematoma-like and diffuse lesions. In this case report, a 71-year-old woman presented with what was assessed as an abscess arising from a traumatic haematoma of the forehead. The lesion was primarily treated conservatively. The condition progressed despite of treatment to a point where the tumour covered a third of her face. After four months, skin biopsies were taken and the diagnosis angiosarcoma was made. This case report should lead to an increased focus on angiosarcomas and the importance of sufficient biopsies.

Late onset ataxia, chorea, and dystonia due to CANVAS.

In this case report, we present a case of a 62-year-old woman with unsteadiness due to CANVAS. In addition to sensory, cerebellar, and vestibular affection she had unusual features in the form of chorea and facial dystonia. Moreover, she had cervical dystonia which, to the best of our knowledge, has not previously been reported in CANVAS.

Tumor-Infiltrating Normal B Cells Revealed by Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic and Crucial for Antitumor Immune Responses in DLBCL.

PURPOSE: Tumor-infiltrating B lymphocytes (TIL-B) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance. EXPERIMENTAL DESIGN: A total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes. The frequencies and numbers of TIL-B clonotypes in individual repertoires were correlated with patient survival, gene expression profiling (GEP) data, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex IHC at single-cell resolution. RESULTS: TIL-B abundance, evaluated by frequencies of normal B-cell clonotypes in the immunoglobulin repertoires, remarkably showed positive associations with significantly better survival of patients in our sequenced cohorts. DLBCLs with high versus low TIL-B abundance displayed distinct GEP signatures, increased pre-memory B-cell state and naïve CD4 T-cell state fractions, and higher CD4+ T-cell infiltration. TIL-B frequency, as a new biomarker in DLBCL, outperformed the germinal center (GC) B-cell-like/activated B-cell-like classification and TIL-T frequency. The identified TIL-B-high GEP signature, including genes upregulated during T-dependent B-cell activation and those highly expressed in normal GC B cells and T cells, showed significant favorable prognostic effects in several external validation cohorts. CONCLUSIONS: TIL-B frequency is a significant prognostic factor in DLBCL and plays a crucial role in antitumor immune responses. This study provides novel insights into the prognostic determinants in DLBCL and TIL-B functions with important therapeutic implications.

Incidence of bony Bankart lesions in Sweden: a study of 790 cases from the Swedish fracture register.

BACKGROUND: A bony Bankart lesion directly affects the stability of the shoulder by reducing the glenoid joint-contact area. The aim of this study was to report on the epidemiological data relating to bony Bankart lesions in Sweden using the Swedish fracture register. The purpose is to evaluate age and sex distribution in the population with bony Bankart lesions, its impact on treatment strategy and further to analyse patient-reported outcomes. METHODS: This was an epidemiological descriptive study. The inclusion criteria were all patients with a unilateral bony Bankart lesion registered between April 2012 and April 2019. The patients' specific data (age, sex, type and time of injury, treatment option and patient-reported outcomes) were extracted from the Swedish fracture register database. RESULTS: A total of 790 unilateral bony Bankart fractures were identified. The majority of the patients were male (58.7%). The median age for all patients at the time of injury was 57 years. Females had a higher median age of 66 years, compared with males, 51 years. Most of the bony Bankart lesions, 662 (91.8%), were registered as a low-energy trauma. More than two-thirds of all treatment registered cases, 509/734 patients (69.3%), were treated non-surgically, 225 (30.7%) were treated surgically, while, in 17 patients (7.5% of all surgically treated patients), the treatment was changed from non-surgical to surgical due to recurrent instability. Surgical treatment was chosen for 149 (35%) of the males and for 76 (25%) of the females. Patient quality of life decreased slightly in both surgically and non-surgically treated groups 1 year after bony Bankart injury. CONCLUSION: This national register-based study provides detailed information on the epidemiology, choice of treatment and patient-reported outcomes in a large cohort of bony Bankart lesions. Most bony Bankart lesions affected males between 40 and 75 years after low-energy falls and non-surgical treatment dominated.

Fracture pattern and risk factors for reoperation after treatment of 156 periprosthetic fractures around an anatomic cemented hip stem.

BACKGROUND AND PURPOSE: The Lubinus SP2 stem has been associated with a very low risk of periprosthetic femoral fractures (PPFFs). We aimed, primarily, to study the radiographic morphology of PPFFs close to a Lubinus SP2 stem. Secondarily, we analyzed whether higher reoperation rate was correlated to the revision method chosen or to the characteristics of the fracture and of the bone. PATIENTS AND METHODS: The study included 156 femoral fractures close to a Lubinus cemented stem. These fractures were treated in 40 hospitals in Sweden between 2006 and 2011 and were followed up until 2019. Data from the Swedish Arthroplasty Register was used. Medical records and radiographs were studied. The fractures were classified according to the Vancouver classification. The fracture location and anatomy were delineated. We also measured the remaining attachment index (RAI) and the canal thickness ratio. RESULTS: Vancouver type C (n = 101) and spiral fractures (n = 67, 41 in Vancouver C and 26 in Vancouver B) were the most common fracture types. 4 fractures were avulsion of the greater trochanter. The remaining 51 fractures occurred around the stem (B1: 25, B2: 16, and B3: 10). B fractures were more commonly reoperated on (18 of 51, 35%) than type C fractures (11 of 101, 11%, P = 0.001). In most femurs with type B3 fracture, the fracture line covered an area only around the stem, but in all B1 and in 11 of 16 B2 fractures, it was extended even distal to the stem. ORIF instead of stem revision in B2 fractures, use of short stems or plates, and inadequate reduction of the fractures were risk factors for subsequent reoperations. CONCLUSION: The higher reoperation rate in type B fractures, compared with fractures distal to the stem, could be caused by their higher degree of complexity and reduced capacity for healing in the region around the stem.

Combined Structural and Plasmonic Enhancement of Nanometer-Thin Film Photocatalysis for Solar-Driven Wastewater Treatment.

Titanium dioxide (TiO2) thin films are commonly used as photocatalytic materials. Here, we enhance the photocatalytic activity of devices based on titanium dioxide (TiO2) by combining nanostructured glass substrates with metallic plasmonic nanostructures. We achieve a three-fold increase of the catalyst's surface area through nanoscale, three-dimensional patterning of periodic, conical grids, which creates a broadband optical absorber. The addition of aluminum and gold activates the structures plasmonically and increases the optical absorption in the TiO2 films to above 70% in the visible and NIR spectral range. We demonstrate the resulting enhancement of the photocatalytic activity with organic dye degradation tests under different light sources. Furthermore, the pharmaceutical drug Carbamazepine, a common water pollutant, is reduced in the aqueous solution by up to 48% in 360 min. Our approach is scalable and potentially enables future solar-driven wastewater treatment.

Acetabular fractures: Epidemiology and mortality based on 2,132 fractures from the Swedish Fracture Register.

Aims: To describe the epidemiology of acetabular fractures including patient characteristics, injury mechanisms, fracture patterns, treatment, and mortality. Methods: We retrieved information from the Swedish Fracture Register (SFR) on all patients with acetabular fractures, of the native hip joint in the adult skeleton, sustained between 2014 and 2020. Study variables included patient age, sex, injury date, injury mechanism, fracture classification, treatment, and mortality. Results: In total, 2,132 patients with acetabular fractures from the SFR were included in the study. The majority of the patients were male (62%) and aged over 70 years old (62%). For patients aged > 70 years, the 30-day mortality was 8% and one-year mortality 24%. For patients aged ≤ 70 years, the 30-day mortality was 0.2% and one-year mortality 2%. Low-energy injuries (63%) and anterior wall fractures (20%) were most common. Treatment was most often non-surgical (75%). Conclusion: The majority of patients who sustain an acetabular fracture are elderly (> 70 years), of male sex, and the fracture most commonly occurs after a simple, low-energy fall. Non-surgical treatment is chosen in the majority of acetabular fracture patients. The one-year mortality for elderly patients with acetabular fracture is similar to the mortality after hip fracture, and a similar multidisciplinary approach to care for these patients should be considered.

The multidisciplinary approach to eosinophilia.

Eosinophilic granulocytes are normally present in low numbers in the bloodstream. Patients with an increased number of eosinophilic granulocytes in the differential count (eosinophilia) are common and can pose a clinical challenge because conditions with eosinophilia occur in all medical specialties. The diagnostic approach must be guided by a thorough medical history, supported by specific tests to guide individualized treatment. Neoplastic (primary) eosinophilia is identified by one of several unique acquired genetic causes. In contrast, reactive (secondary) eosinophilia is associated with a cytokine stimulus in a specific disease, while idiopathic eosinophilia is a diagnosis by exclusion. Rational treatment is disease-directed in secondary cases and has paved the way for targeted treatment against the driver in primary eosinophilia, whereas idiopathic cases are treated as needed by principles in eosinophilia originating from clonal drivers. The vast majority of patients are diagnosed with secondary eosinophilia and are managed by the relevant specialty-e.g., rheumatology, allergy, dermatology, gastroenterology, pulmonary medicine, hematology, or infectious disease. The overlap in symptoms and the risk of irreversible organ involvement in eosinophilia, irrespective of the cause, warrants that patients without a diagnostic clarification or who do not respond to adequate treatment should be referred to a multidisciplinary function anchored in a hematology department for evaluation. This review presents the pathophysiology, manifestations, differential diagnosis, diagnostic workup, and management of (adult) patients with eosinophilia. The purpose is to place eosinophilia in a clinical context, and therefore justify and inspire the establishment of a multidisciplinary team of experts from diagnostic and clinical specialties at the regional level to support the second opinion. The target patient population requires highly specialized laboratory analysis and therapy and occasionally has severe eosinophil-induced organ dysfunction. An added value of a centralized, clinical function is to serve as a platform for education and research to further improve the management of patients with eosinophilia. Primary and idiopathic eosinophilia are key topics in the review, which also address current research and discusses outstanding issues in the field.

Cell-free DNA for detection of clonal B cells in diffuse large B cell lymphoma by sequencing.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in the western world. It is highly heterogeneous with a variable clinical course, but curable with chemo-immunotherapy in up to 70% of all cases. The lymphoma presents in lymph nodes and/or extranodal lymphoid tissue, and the diagnosis is based on invasive procedures for histopathologic evaluation. METHODS: In this technical study, we evaluated cell-free DNA (cfDNA) from blood plasma to detect clonal B cells in patients with DLBCL using rearranged immunoglobulin heavy chain gene as targets by next-generation sequencing. Clonal B cell sequences and frequencies were determined from blood plasma cfDNA and cellular DNA from matched excised lymphoma tissues and mononuclear cells isolated from diagnostic bone marrow and blood samples from 15 patients. RESULTS: We showed that identical clonal rearrangements could be detected in blood plasma and excised lymphoma tissue and that plasma cfDNA was superior in detecting clonal rearrangements compared to blood or bone marrow-derived cellular DNA. CONCLUSION: These findings consolidate the role of blood plasma as a reliable and easily accessible source for detecting neoplastic cells in DLBCL.

Variation in gene expression along an elevation gradient of Rhododendron sanguineum var. haemaleum assessed in a comparative transcriptomic analysis.

Selection along environmental gradients may play a vital role in driving adaptive evolution. Nevertheless, genomic variation and genetic adaptation along environmental clines remains largely unknown in plants in alpine ecosystems. To close this knowledge gap, we assayed transcriptomic profiles of late flower bud and early leaf bud of Rhododendron sanguineum var. haemaleum from four different elevational belts between 3,000 m and 3,800 m in the Gaoligong Mountains. By comparing differences in gene expression of these samples, a gene co-expression network (WGCNA) was constructed to identify candidate genes related to elevation. We found that the overall gene expression patterns are organ-specific for the flower and leaf. Differentially expressed unigenes were identified in these organs. In flowers, these were mainly related to terpenoid metabolism (RsHMGR, RsTPS), while in leaves mainly related to anthocyanin biosynthesis (RsCHS, RsF3'5'H). Terpenoids are the main components of flower scent (fragrance) likely attracting insects for pollination. In response to fewer pollinators at higher elevation zone, it seems relatively less scent is produced in flower organs to reduce energy consumption. Secondary metabolites in leaves such as anthocyanins determine the plants' alternative adaptive strategy to extreme environments, such as selective pressures of insect herbivory from environmental changes and substrate competition in biosynthesis pathways at high elevations. Our findings indicated that the gene expression profiles generated from flower and leaf organs showed parallel expression shifts but with different functionality, suggesting the existence of flexibility in response strategies of plants exposed to heterogeneous environments across elevational gradients. The genes identified here are likely to be involved in the adaptation of the plants to these varying mountainous environments. This study thus contributes to our understanding of the molecular mechanisms of adaptation in response to environmental change.